Multivalent cross-linking of actin filaments and microtubules through the microtubule-associated protein Tau

In the paper

“This is particularly the case for the interaction with filamentous actin, which plays an important role in dendritic spine morphology and postsynaptic reorganizations23.”

What the sources say

• Supported

  The “Actin organization in dendritic spines” section says that F-actin levels affect spine morphology and that actin stabilizes postsynaptic proteins and modulates spine-head structure in response to postsynaptic signaling. The section on actin dynamics also links synaptic plasticity to reorganization of the spine actin cytoskeleton. Page numbers were not provided in our copy. (LLM, conf=0.92)

  cites [23] Hotulainen, P. & Hoogenraad, C. C. Actin in dendritic spines: connecting dynamics to function. J. Cell. Biol. 189, 619–629 (2010). source

In the paper

“In addition, acetylation of Tau modulates actin polymerization and enhances synaptic dysfunction26.”

What the sources say

• Supported

  The Discussion states that acetylated tau blocks activity-induced F-actin assembly and inhibits synaptic potentiation. The Results section likewise reports disrupted activity-dependent actin polymerization and impaired synaptic plasticity in mice expressing acetylation-mimicking tau. No page numbers are provided in the supplied copy. (LLM, conf=0.94)

  cites [26] Tracy, T. E. et al. Acetylated Tau obstructs KIBRA-mediated signaling in synaptic plasticity and promotes tauopathy-related memory loss. Neuron 90, 245–260 (2016). source

In the paper

“Misfolding and aberrant accumulation of Tau is a pathological hallmark of Alzheimer’s disease (AD)18, 19.”

What the sources say

• ?Not checked — no full text of the sourcecites [18] Williams, D. R. Tauopathies: classification and clinical update on neurodegenerative diseases associated with microtubule-associated protein tau. Intern. Med. J. 36, 652–660 (2006). source
• Supported

  The Abstract states that Alzheimer’s disease is defined by abundant neurofibrillary lesions and that those lesions are made of Tau filaments. The Neuropathological characteristics section also reports abundant tangles and pathological, aggregated Tau in AD brain, supporting the paraphrase. (LLM, conf=0.92)

  cites [19] Fitzpatrick, A. W. P. et al. Cryo-EM structures of tau filaments from Alzheimer’s disease. Nature 547, 185–190 (2017). source

In the paper

“Tau occurs in six different isoforms in the human central nervous system13, 14.”

What the sources say

• ?Not checked — no full text of the sourcecites [13] Gustke, N., Trinczek, B., Biernat, J., Mandelkow, E. M. & Mandelkow, E. Domains of tau protein and interactions with microtubules. Biochemistry 33, 9511–9522 (1994). source
• Partly supported

  The Introduction (p. 717) describes tau isolated from adult brain as six related phosphopeptides and discusses several tau isoforms. It does not establish that six distinct isoforms occur in the human central nervous system; it says phosphatase treatment reduces the number of resolvable forms to four. (LLM, conf=0.82)

  cites [14] Butner, K. A. & Kirschner, M. W. Tau protein binds to microtubules through a flexible array of distributed weak sites. J. Cell. Biol. 115, 717–730 (1991). sourceExperimental — accuracy not yet measured

In the paper

“The Tau isoforms differ in the number of N-terminal inserts and have either three or four imperfect repeats in their C-terminal half15.”

What the sources say

• ?Could not verify

  The Results and Discussion passages describe tau’s role in microtubule assembly, not the structures of tau isoforms. Searches for N-terminal inserts, three or four C-terminal repeats, and alternative splicing found no passage addressing the claim. Page numbers were not available in our copy. (LLM, conf=0.76)

  cites [15] Weingarten, M. D., Lockwood, A. H., Hwo, S. Y. & Kirschner, M. W. A protein factor essential for microtubule assembly. Proc. Natl Acad. Sci. USA 72, 1858–1862 (1975). sourceExperimental — accuracy not yet measured

In the paper

“The interaction of MAPs with actin is important for neurite outgrowth11, 12.”

What the sources say

• ?Could not verify

  The paper reports that tau expression induces long processes in nonneuronal Sf9 cells and, separately, that cytochalasin treatment produces short retraction processes by disrupting the actin network. The passages on process formation and cytochalasin do not address whether MAPs interact with actin or whether such an interaction is important for neurite outgrowth (searched: actin interaction, tau actin cytoskeleton). (LLM, conf=0.72)

  cites [11] Knops, J. et al. Overexpression of tau in a nonneuronal cell induces long cellular processes. J. Cell. Biol. 114, 725–733 (1991). sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction says MAPs regulate microtubules involved in neurite growth. In “A Model Relating tau Phosphorylation to Process Formation” (page unavailable), the paper says MAP interactions with cytoskeletal elements are important in process formation and separately mentions softening of the actin cortex. It does not specifically say that MAP–actin interactions are important for neurite outgrowth. (LLM, conf=0.81)

  cites [12] Biernat, J. & Mandelkow, E. M. The development of cell processes induced by tau protein requires phosphorylation of serine 262 and 356 in the repeat domain and is inhibited by phosphorylation in the proline-rich domains. Mol. Biol. Cell. 10, 727–740 (1999). sourceExperimental — accuracy not yet measured

In the paper

“Because a single repeat interacts with both monomeric and filamentous actin, but does not bundle actin filaments, more than one microtubule-binding repeat is believed to be required for bundling of filamentous actin (F-actin)17.”

What the sources say

• Partly supported

  The Results (page not provided) show that a peptide containing one tubulin-binding repeat binds G-actin and F-actin but does not bundle filaments. The authors suggest that bundling may require more than one actin-binding site; they do not establish that those sites must be multiple microtubule-binding repeats. (LLM, conf=0.85)

  cites [17] Correas, I., Padilla, R. & Avila, J. The tubulin-binding sequence of brain microtubule-associated proteins, tau and MAP-2, is also involved in actin binding. Biochem. J. 269, 61–64 (1990). sourceExperimental — accuracy not yet measured

In the paper

“Because a single repeat interacts with both monomeric and filamentous actin, but does not bundle actin filaments, more than one microtubule-binding repeat is believed to be required for bundling of filamentous actin (F-actin)17.”

What the sources say

• Supported

  The Introduction identifies the synthetic tau peptide as one tubulin-binding-site repeat. The Results state that it binds both G-actin and F-actin but cannot bundle actin filaments, and suggest that bundling may require more than one actin-binding site. (LLM, conf=0.94)

  cites [17] Correas, I., Padilla, R. & Avila, J. The tubulin-binding sequence of brain microtubule-associated proteins, tau and MAP-2, is also involved in actin binding. Biochem. J. 269, 61–64 (1990). source

In the paper

“In addition, MAPs bundle actin filaments and cross-link the cellular cytoskeleton formed by microtubules and actin filaments (Fig. 1a)3–10.”

What the sources say

• ?Not checked — no full text of the sourcecites [3] Yamauchi, P. S. & Purich, D. L. Microtubule-associated protein interactions with actin filaments: evidence for differential behavior of neuronal MAP-2 and tau in the presence of phosphatidyl-inositol. Biochem. Biophys. Res. Commun. 190, 710–715 (1993). source
• Partly supported

  The Results and Discussion show that tau, a microtubule-associated protein, bundles F-actin. The Discussion describes tau and MAP2c as potential cross-linkers between microtubules and actin, but does not establish the citing sentence’s categorical claim that MAPs cross-link those networks in cells. (LLM, conf=0.83)

  cites [4] He, H. J. et al. The proline-rich domain of tau plays a role in interactions with actin. BMC Cell. Biol. 10, 81 (2009). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [5] Sattilaro, R. F. Interaction of microtubule-associated protein 2 with actin filaments. Biochemistry 25, 2003–2009 (1986). source
• ?Not checked — no full text of the sourcecites [6] Selden, S. C. & Pollard, T. D. Phosphorylation of microtubule-associated proteins regulates their interaction with actin filaments. J. Biol. Chem. 258, 7064–7071 (1983). source
• Supported

  The Results section (“Tau simultaneously binds to microtubules and actin filaments”; page unavailable) reports that tau, a microtubule-associated protein, forms F-actin bundles. The Results section (“Tau coordinates dynamic microtubules and actin filaments”; page unavailable) also measures tau’s microtubule–actin cross-linking activity. These in vitro findings support the claim as an example of what a MAP can do. (LLM, conf=0.90)

  cites [7] Elie, A. et al. Tau co-organizes dynamic microtubule and actin networks. Sci. Rep. 5, 9964 (2015). source
• ?Not checked — no full text of the sourcecites [8] Griffith, L. M. & Pollard, T. D. The interaction of actin filaments with microtubules and microtubule-associated proteins. J. Biol. Chem. 257, 9143–9151 (1982). source
• Partly supported

  The Discussion (page unavailable) says MAPs can interact with the actin cytoskeleton and may regulate microtubule bundling. It does not say MAPs bundle actin filaments or cross-link actin filaments with microtubules; the cited bundling concerns microtubules, not actin. (LLM, conf=0.85)

  cites [9] Biernat, J. et al. Protein kinase MARK/PAR-1 is required for neurite outgrowth and establishment of neuronal polarity. Mol. Biol. Cell. 13, 4013–4028 (2002). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section (‘MAP2c Causes Actin Gelation In Vitro’; page unavailable) reports that MAP2c forms actin bundles at higher concentrations or lower ionic strength. But the Discussion (‘In Vivo Functions of MAP2c’; page unavailable) explicitly says the data cannot determine whether MAP2c cross-links microtubules to actin filaments. The claim presents that cross-linking as established for MAPs generally. (LLM, conf=0.90)

  cites [10] Cunningham, C. C. et al. Microtubule-associated protein 2c reorganizes both microtubules and microfilaments into distinct cytological structures in an actin-binding protein-280-deficient melanoma cell line. J. Cell. Biol. 136, 845–857 (1997). sourceExperimental — accuracy not yet measured

In the paper

“One of these binding partners is cofilin, a 21 kDa eukaryotic protein, which binds to F-actin with a K d < 0.05 µM33 and results in disassembly of F-actin34, 35.”

What the sources say

• ?Not checked — no full text of the sourcecites [33] Bobkov, A. A. et al. Structural effects of cofilin on longitudinal contacts in F-actin. J. Mol. Biol. 323, 739–750 (2002). source
• Partly supported

  The Cofilin section (page not provided) describes cofilin as a 21 kDa protein that binds F-actin, supporting that part of the statement attributed to this source. It does not give the cited F-actin Kd of <0.05 µM; its reported dissociation constant of 0.1–0.2 µM is for binding to monomeric actin. The separate disassembly statement carries other citations. (LLM, conf=0.88)

  cites [34] Yonezawa, N. et al. Distribution among tissues and intracellular localization of cofilin, a 21kDa actin-binding protein. Cell. Struct. Funct. 12, 443–452 (1987). sourceExperimental — accuracy not yet measured
• Partly supported

  Citation 33 is attached to the Kd claim. In Results and Discussion (‘Bound ADF/cofilin dissociates slowly from actin filaments’; page unavailable), the paper reports rapid binding to bare actin filaments and high overall binding affinity, but gives no Kd below 0.05 µM. The disassembly clause is assigned to citations 34 and 35, not this source. (LLM, conf=0.84)

  cites [35] Suarez, C. et al. Cofilin tunes the nucleotide state of actin filaments and severs at bare and decorated segment boundaries. Curr. Biol. 21, 862–868 (2011). sourceExperimental — accuracy not yet measured

In the paper

“Although actin contains five cysteine residues, a number of studies has shown that the C-terminal C374, which is in close proximity to actin’s hydrophobic pocket (Fig. 2d), is most solvent exposed (Supplementary Fig. 4a, b) and incorporates more than 70% of spin labels during spin labeling reactions37–41.”

What the sources say

• ?Not checked — no full text of the sourcecites [37] Yasunaga, T. & Wakabayashi, T. Relocation of Cys374 of actin induced by labeling with fluorescent dyes. J. Biochem. 129, 201–204 (2001). source
• Partly supported

  The section “Rotational motions in actin observed by spin labels” states that Cys-374 incorporated more than 70% of maleimide spin labels under the conditions used in the paper. Our copy does not state that actin has five cysteine residues, and the reported percentage is specific to those labeling conditions rather than spin labeling generally. (LLM, conf=0.86)

  cites [38] Kupi, T., Grof, P., Nyitrai, M. & Belagyi, J. The uncoupling of the effects of formins on the local and global dynamics of actin filaments. Biophys. J. 96, 2901–2911 (2009). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [39] Mossakowska, M., Belagyi, J. & Strzelecka-Golaszewska, H. An EPR study of the rotational dynamics of actins from striated and smooth muscle and their complexes with heavy meromyosin. Eur. J. Biochem. 175, 557–564 (1988). source
• ?Not checked — no full text of the sourcecites [40] Thomas, D. D., Seidel, J. C. & Gergely, J. Rotational dynamics of spin-labeled F-actin in the sub-millisecond time range. J. Mol. Biol. 132, 257–273 (1979). source
• ?Not checked — no full text of the sourcecites [41] Yoshimura, H. et al. Torsional motion of eosin-labeled F-actin as detected in the time-resolved anisotropy decay of the probe in the sub-millisecond time range. J. Mol. Biol. 179, 453–467 (1984). source

In the paper

“In addition to phosphorylation, acetylation of Tau at K281, a residues that is located in an F-actin interacting helix of Tau (Fig. 3d), affects the interaction of Tau with actin and modulate Tau-mediated toxicity26.”

What the sources say

• Partly supported

  The Results report that an acetylation-mimicking K274/K281 tau mutant interacted less with F-actin than wild-type tau; the Discussion links that mutant to synaptic dysfunction and memory deficits. The paper does not establish that K281 alone has these effects or describe K281 as located in an F-actin-interacting helix. Its evidence for altered tau–actin binding comes from the double mutant, not directly from acetylated tau. (LLM, conf=0.88)

  cites [26] Tracy, T. E. et al. Acetylated Tau obstructs KIBRA-mediated signaling in synaptic plasticity and promotes tauopathy-related memory loss. Neuron 90, 245–260 (2016). sourceExperimental — accuracy not yet measured

In the paper

“In addition, Tau-induced neurotoxicity is associated with increased F-actin levels22, and Tau-induced remodeling of the actin cytoskeleton can cause plasma membrane blebbing57.”

What the sources say

• Supported

  The Results (Fig. 3, p. 471) describe F-actin remodeling alongside bleb formation in Tau-expressing C6 glial cells. The Discussion (p. 478) concludes that F-actin regulates formation of these blebs, supported by their disappearance when F-actin was disrupted and reappearance after the drug was removed. (LLM, conf=0.93)

  cites [57] Torres-Cruz, F. M. et al. Expression of Tau produces aberrant plasma membrane blebbing in glial cells through RhoA-ROCK-dependent F-actin remodeling. J. Alzheimers Dis. 52, 463–482 (2016). source

In the paper

“Tau colocalizes with actin in differentiating PC12 cells68, N2a cells69 and in the postsynaptic compartments of mature neurons70.”

What the sources say

• ?Not checked — no full text of the sourcecites [68] Yu, J. Z. & Rasenick, M. M. Tau associates with actin in differentiating PC12 cells. FASEB J. 20, 1452–1461 (2006). source
• Partly supported

  The Results (page unavailable) report tau-positive processes and altered F-actin organization in differentiating N2a cells. They do not report that tau and actin colocalize; the cited paper supports their presence in these cells, but not the specific spatial relationship attributed to it. Citation 69 is attached only to the N2a-cell portion of the sentence. (LLM, conf=0.84)

  cites [69] Sontag, J. M., Nunbhakdi-Craig, V., Mitterhuber, M., Ogris, E. & Sontag, E. Regulation of protein phosphatase 2A methylation by LCMT1 and PME-1 plays a critical role in differentiation of neuroblastoma cells. J. Neurochem. 115, 1455–1465 (2010). sourceExperimental — accuracy not yet measured
• Partly supported

  For citation 70, the 'Missorting of tau and effects on synapses' section (Fig. 1; page not provided) reports that F-actin fills postsynaptic spine heads and that expressed tau enters those spine heads in hippocampal neurons with mature synapses. The claim omits the crucial condition: tau was experimentally expressed and missorted; in untransfected neurons, the paper reports tau only in axons. Citations 68 and 69, attached to the PC12 and N2a claims, are not assessed here. (LLM, conf=0.87)

  cites [70] Thies, E. & Mandelkow, E. M. Missorting of tau in neurons causes degeneration of synapses that can be rescued by the kinase MARK2/Par-1. J. Neurosci. 27, 2896–2907 (2007). sourceExperimental — accuracy not yet measured

In the paper

“The hexapeptide populates extended structure in solution27, is found in cross-β structure in amyloid fibrils63, but folds into helical structure in complex with F-actin (Fig. 3d).”

What the sources say

• Supported

  The citation to this paper is attached to the claim that the hexapeptide populates extended structure in solution, not to the fibril or F-actin claims. In Results, “Secondary Structure Propensity in 441-Residue Tau,” the paper reports increased positive coupling values for the region containing 275VQIINK280, which it identifies as indicating extended or β-structure propensity. (LLM, conf=0.92)

  cites [27] Mukrasch, M. D. et al. Structural polymorphism of 441-residue tau at single residue resolution. PLoS Biol. 7, e34 (2009). source
• ?Not checked — no full text of the sourcecites [63] Andronesi, O. C. et al. Characterization of Alzheimer’s-like paired helical filaments from the core domain of tau protein using solid-state NMR spectroscopy. J. Am. Chem. Soc. 130, 5922–5928 (2008). source

In the paper

“In addition, phosphorylated Tau is recruited to actin-cofilin rods, which might lead to neuropil threads56.”

What the sources say

• Supported

  The Discussion says cofilin-actin rods may trigger the sequestration and accumulation of Ser262/356-phosphorylated tau in some neuropil threads. It also proposes that the rods serve as a template for pMAP recruitment, matching the claim’s tentative wording. (LLM, conf=0.93)

  cites [56] Whiteman, I. T. et al. Activated actin-depolymerizing factor/cofilin sequesters phosphorylated microtubule-associated protein during the assembly of Alzheimer-like neuritic cytoskeletal striations. J. Neurosci. 29, 12994–13005 (2009). source

In the paper

“Analysis of secondary structure in the lowest energy conformation using STRIDE47, identifies α-helix for residues 261–268 and 3–10 helix for residues 277–280.”

What the sources say

• Supported

  The citation identifies STRIDE as the tool used for secondary-structure analysis; it does not attribute the Tau residue assignments to the STRIDE paper. The Abstract identifies STRIDE as a tool for assigning secondary structure from protein atomic coordinates, and the STRIDE WEB SERVER AND DATABASE section describes its per-residue assignments. The residue assignments are the citing authors’ own result. (LLM, conf=0.93)

  cites [47] Heinig, M. & Frishman, D. STRIDE: a web server for secondary structure assignment from known atomic coordinates of proteins. Nucleic Acids Res. 32, W500–W502 (2004). source

In the paper

“In addition, the N-terminal halves of each of Tau’s four 18-residue aminoacid repeats64 bind to F-actin’s hydrophobic pocket and fold into helical structure (Fig. 3c; Supplementary Figs. 12 and 14).”

What the sources say

• Supported

  The citation is attached to the description of tau’s four 18-residue repeats, not to the subsequent F-actin binding and helical-structure findings, which the citing sentence points to its own figures. The Introduction states that tau contains either three or four copies of a conserved 18-amino-acid repeat. (LLM, conf=0.91)

  cites [64] Goode, B. L. & Feinstein, S. C. Identification of a novel microtubule binding and assembly domain in the developmentally regulated inter-repeat region of tau. J. Cell. Biol. 124, 769–782 (1994). source

In the paper

“The interaction of Tau with actin is important for neurite outgrowth and synaptic dysfunction11, 12, 22.”

What the sources say

• Partly supported

  The Introduction (p. 725) links tau to neurite elongation, and the discussion reports that tau-expressing Sf9 cells developed long processes. The paper does not establish that tau’s interaction with actin drives outgrowth or synaptic dysfunction; it says synaptic vesicles were not observed in those processes. (LLM, conf=0.86)

  cites [11] Knops, J. et al. Overexpression of tau in a nonneuronal cell induces long cellular processes. J. Cell. Biol. 114, 725–733 (1991). sourceExperimental — accuracy not yet measured
• Partly supported

  The introduction and 'A Model Relating tau Phosphorylation to Process Formation' (page unavailable) link tau to neurite or cell-process outgrowth and mention softening of the actin cortex before a process forms. They do not establish that a tau–actin interaction drives outgrowth, and they do not address synaptic dysfunction. (LLM, conf=0.83)

  cites [12] Biernat, J. & Mandelkow, E. M. The development of cell processes induced by tau protein requires phosphorylation of serine 262 and 356 in the repeat domain and is inhibited by phosphorylation in the proline-rich domains. Mol. Biol. Cell. 10, 727–740 (1999). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [22] Fulga, T. A. et al. Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo. Nat. Cell. Biol. 9, 139–148 (2007). source

In the paper

“Cys374 of actin is solvent exposed and can be labeled with the spin label MTSSL37–41.”

What the sources say

• ?Not checked — no full text of the sourcecites [37] Yasunaga, T. & Wakabayashi, T. Relocation of Cys374 of actin induced by labeling with fluorescent dyes. J. Biochem. 129, 201–204 (2001). source
• Partly supported

  The Introduction and “Rotational motions in actin observed by spin labels” report that a spin label attaches to Cys-374 and that this site incorporated more than 70% of the labels under the experimental conditions. This supports its accessibility for labeling, but the paper uses maleimide spin label (MSL), not MTSSL, and does not explicitly describe Cys-374 as solvent exposed. Page numbers were not available in our copy. (LLM, conf=0.88)

  cites [38] Kupi, T., Grof, P., Nyitrai, M. & Belagyi, J. The uncoupling of the effects of formins on the local and global dynamics of actin filaments. Biophys. J. 96, 2901–2911 (2009). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [39] Mossakowska, M., Belagyi, J. & Strzelecka-Golaszewska, H. An EPR study of the rotational dynamics of actins from striated and smooth muscle and their complexes with heavy meromyosin. Eur. J. Biochem. 175, 557–564 (1988). source
• ?Not checked — no full text of the sourcecites [40] Thomas, D. D., Seidel, J. C. & Gergely, J. Rotational dynamics of spin-labeled F-actin in the sub-millisecond time range. J. Mol. Biol. 132, 257–273 (1979). source
• ?Not checked — no full text of the sourcecites [41] Yoshimura, H. et al. Torsional motion of eosin-labeled F-actin as detected in the time-resolved anisotropy decay of the probe in the sub-millisecond time range. J. Mol. Biol. 179, 453–467 (1984). source

In the paper

“Pathogenic forms of Tau have been connected to the formation of actin-rich rods56, which were found to induce neurodegeneration in Drosophila neurons22.”

What the sources say

• Supported

  The citation to this paper is attached to the connection between pathogenic tau and actin-rich rods, not the later claim about neurodegeneration in Drosophila neurons. The Abstract reports that cofilin-actin rods recruit phosphorylated tau in cultured neurons, and the Discussion describes tau sequestration in those rods as a possible early pathogenic event. (LLM, conf=0.91)

  cites [56] Whiteman, I. T. et al. Activated actin-depolymerizing factor/cofilin sequesters phosphorylated microtubule-associated protein during the assembly of Alzheimer-like neuritic cytoskeletal striations. J. Neurosci. 29, 12994–13005 (2009). source
• ?Not checked — no full text of the sourcecites [22] Fulga, T. A. et al. Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo. Nat. Cell. Biol. 9, 139–148 (2007). source

In the paper

“For example, a C-terminal fragment and a peptide corresponding to the second microtubule-binding repeat bind actin, but are incapable of mediating actin cross-linking5, 17.”

What the sources say

• ?Not checked — no full text of the sourcecites [5] Sattilaro, R. F. Interaction of microtubule-associated protein 2 with actin filaments. Biochemistry 25, 2003–2009 (1986). source
• Partly supported

  The Results report that the synthetic tau peptide binds G-actin and F-actin but does not bundle actin filaments. The Introduction and Discussion describe it as corresponding to one tubulin-binding repeat, without identifying it as the second. They report that a 32 kDa MAP-2 fragment binds actin, but do not establish that this C-terminal fragment cannot cross-link actin. (LLM, conf=0.86)

  cites [17] Correas, I., Padilla, R. & Avila, J. The tubulin-binding sequence of brain microtubule-associated proteins, tau and MAP-2, is also involved in actin binding. Biochem. J. 269, 61–64 (1990). sourceExperimental — accuracy not yet measured

In the paper

“In agreement with previous findings, we show that Tau binds with high-affinity to filamentous actin, resulting in F-actin bundling (Fig. 1b).”

In the paper

“Addition of an equimolar concentration of Tau caused bundling of F-actin (Fig. 1b), although some single filaments remained.”

In the paper

“Tau and cofilin helices is well conserved, but the directionality of their polypeptide chain is inverted (Fig. 3e, f).”

In the paper

“Haddock clustered 192 complex structures in four clusters, representing 96.0% of the water-refined Haddock models.”

In the paper

“Both the proline-rich region and the microtubule-binding repeats contribute to the interaction (Figs. 1e, f).”

In the paper

“Docking of experimentally determined Tau helices to the F-actin surface together with sequence alignment showed that the overall position of the interacting Tau and cofilin helices is well conserved, but the directionality of their polypeptide chain is inverted (Fig. 3e, f).”

In the paper

“MAPs such as Tau belong to the class of intrinsically disordered proteins, which do not fold into a stable three-dimensional structure28.”

What the sources say

• ?Not checked — no full text of the sourcecites [28] Dyson, H. J. & Wright, P. E. Intrinsically unstructured proteins and their functions. Nat. Rev. Mol. Cell. Biol. 6, 197–208 (2005). source

In the paper

“Proteins from the MAP2 family also bind to actin filaments through their repeat domain8.”

What the sources say

• ?Not checked — no full text of the sourcecites [8] Griffith, L. M. & Pollard, T. D. The interaction of actin filaments with microtubules and microtubule-associated proteins. J. Biol. Chem. 257, 9143–9151 (1982). source

In the paper

“Microtubule-associated proteins (MAPs) bind to stabilize and promote assembly of microtubules1, 2.”

What the sources say

• ?Not checked — no full text of the sourcecites [1] Mandelkow, E. & Mandelkow, E. M. Microtubules and microtubule-associated proteins. Curr. Opin. Cell. Biol. 7, 72–81 (1995). source
• ?Not checked — no full text of the sourcecites [2] Lee, G. Non-motor microtubule-associated proteins. Curr. Opin. Cell. Biol. 5, 88–94 (1993). source

In the paper

“Cryo-electron microscopy further showed that the binding site of cofilin on F-actin is highly similar to its binding site on G-actin (Fig. 2a)32.”

What the sources say

• ?Not checked — no full text of the sourcecites [32] Carlier, M. F. & Pantaloni, D. Control of actin dynamics in cell motility. J. Mol. Biol. 269, 459–467 (1997). source

In the paper

“Moreover the tight connection between microtubules and actin drives the guided extension of axons during neuronal development as well as the formation and activity of synapses in mature neurons67.”

What the sources say

• ?Not checked — no full text of the sourcecites [67] Hoogenraad, C. C. & Bradke, F. Control of neuronal polarity and plasticity--a renaissance for microtubules? Trends Cell. Biol. 19, 669–676 (2009). source

In the paper

“Notably, the conformations that are induced in Tau upon binding to F-actin and microtubules are very different, because F-actin interaction is connected to helix formation (Fig. 3), while short Tau regions fold into a hairpin-like structure in complex with microtubules46.”

What the sources say

• ?Not checked — no full text of the sourcecites [46] Kadavath, H. et al. Folding of the tau protein on microtubules. Angew. Chem. Int. Ed. Engl. 54, 10347–10351 (2015). source

In the paper

“We showed that Tau utilizes a structural mechanism for binding to actin filaments, which is used by many actin-binding proteins, but allows a highly dynamic and multivalent interaction with both actin filaments and microtubules.”

In the paper

“These data support a role for Tau as regulator of microtubules and actin and suggests its potential role as linker between the both cytoskeletons.”

In the paper

“The F-actin-interacting Tau residues are separated from each other by flexible linkers, which enable a high degree of dynamics and multivalency in the Tau/F-actin interaction.”

In the paper

“The interaction between actin filaments and microtubules is important for cellular processes including cell division, vesicle and organelle transport, axonal growth and migration66.”

What the sources say

• ?Not checked — no full text of the sourcecites [66] Rodriguez, O. C. et al. Conserved microtubule-actin interactions in cell movement and morphogenesis. Nat. Cell. Biol. 5, 599–609 (2003). source

In the paper

“Taken together the data demonstrate that bundling of filamentous actin and cross-linking of the cellular cytoskeleton depend on the metamorphic and multivalent nature of microtubule-associated proteins.”

In the paper

“Tau undergoes several post-translational modifications that influence its function, aggregation and toxicity73.”

What the sources say

• ?Not checked — no full text of the sourcecites [73] Gong, C. X., Liu, F., Grundke-Iqbal, I. & Iqbal, K. Post-translational modifications of tau protein in Alzheimer’s disease. J. Neural Transm. 112, 813–838 (2005). source

In the paper

“An important post-translational modification is phosphorylation, because Tau is hyperphosphorylated in the brains of patients with Alzheimer’s disease74.”

What the sources say

• ?Not checked — no full text of the sourcecites [74] Bancher, C. et al. Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer’s disease. Brain Res. 477, 90–99 (1989). source

In the paper

“Optimal sequence alignment was achieved, when the sequence of Tau was inverted (Fig. 3f), suggesting an inverted orientation of its recognition helix when compared to cofilin (Fig. 3e; Supplementary Fig. 9).”

In the paper

“Thus, phosphorylation of Tau at KXGS motifs fosters the interaction with actin-containing structures, but attenuates the direct interaction of Tau with microtubules and F-actin.”