CoChat
Sign Up
Cited by 76

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

An Organelle Gatekeeper Function for Caenorhabditis elegans UNC-16 (JIP3) at the Axon Initial Segment

Edwards, Stacey L, Yu, Szi-chieh, Hoover, Christopher M, Phillips, Barret C, Richmond, Janet E, Miller, Kenneth G·2013·Genetics
DOI 10.1534/genetics.112.147348
Open this paper in CoChat — free account

Abstract

Neurons must cope with extreme membrane trafficking demands to produce axons with organelle compositions that differ dramatically from those of the cell soma and dendrites; however, the mechanism by which they accomplish this is not understood. Here we use electron microscopy and quantitative imaging of tagged organelles to show that Caenorhabditis elegans axons lacking UNC-16 (JIP3/Sunday Driver) accumulate Golgi, endosomes, and lysosomes at levels up to 10-fold higher than wild type, while ER membranes are largely unaffected. Time lapse microscopy of tagged lysosomes in living animals and an analysis of lysosome distributions in various regions of unc-16 mutant axons revealed that UNC-16 inhibits organelles from escaping the axon initial segment (AIS) and moving to the distal synaptic part of the axon. Immunostaining of native UNC-16 in C. elegans neurons revealed a localized concentration of UNC-16 at the initial segment, although UNC-16 is also sparsely distributed in distal regions of axons, including the synaptic region. Organelles that escape the AIS in unc-16 mutants show bidirectional active transport within the axon commissure that occasionally deposits them in the synaptic region, where their mobility decreases and they accumulate. These results argue against the long-standing, untested hypothesis that JIP3/Sunday Driver promotes anterograde organelle transport in axons and instead suggest an organelle gatekeeper model in which UNC-16 (JIP3/Sunday Driver) selectively inhibits the escape of Golgi and endosomal organelles from the AIS. This is the first evidence for an organelle gatekeeper function at the AIS, which could provide a regulatory node for controlling axon organelle composition.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1534/genetics.112.147348

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • UNC-16-deficient worms show a clearly aggravated phenotype, including uncoordinated movement, which is not the case for Y71H2AM.2(null) worms.

    “However, UNC-16-deficient worms show a clearly aggravated phenotype, including uncoordinated movement, which is not the case for Y71H2AM.2(null)worms”

    From TMEM55B promotes anterograde transport and distal axonal distribution of LAMP1-positive organelles (2026) · cites this paper as Edwards et al., 2013

    The Results report that three unc-16 mutants had sluggish locomotion rates of about 15% of wild type, supporting a substantial movement defect. The paper does not report a phenotype for Y71H2AM.2(null) worms, so it does not support the comparison between the mutants. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The phenotype of Y71H2AM.2(null) worms reflects in many regards that of worms depleted of the JIP3/4 homolog UNC-16, in particular the redistribution of lysosomes to the more proximal axon.

    “The phenotype of the Y71H2AM.2(null)worms interestingly reflects in many regards that of worms depleted of the JIP3/4 homolog UNC-16 (the C. elegans homolog of JIP3/4), in particular the redistribution of lysosomes to the more proximal axon (Celestino et al., 2022;Edwards et al., 2015;Edwards et al., 2013)”

    From TMEM55B promotes anterograde transport and distal axonal distribution of LAMP1-positive organelles (2026) · cites this paper as Edwards et al., 2013

  • UNC-16 localization is concentrated at the initial segment in worms, suggesting attachment to cargo in this area.

    “UNC-16 localization, which is concentrated at the initial segment in worms (Edwards et al., 2013), suggesting attachment to cargo in this area.”

    From TMEM55B promotes anterograde transport and distal axonal distribution of LAMP1-positive organelles (2026) · cites this paper as Edwards et al., 2013

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 53

  1. Arimoto, 2011, The Caenorhabditis elegans JIP3 protein UNC-16 functions as an adaptor to link kinesin-1 with cytoplasmic dynein., J. Neurosci., 31, 2216, 10.1523/JNEUROSCI.2653-10.2011 · DOI
  2. Bonanomi, 2006, Protein sorting in the synaptic vesicle life cycle., Prog. Neurobiol., 80, 177, 10.1016/j.pneurobio.2006.09.002 · DOI
  3. Bowman, 2000, Kinesin-dependent axonal transport is mediated by the sunday driver (SYD) protein., Cell, 103, 583, 10.1016/S0092-8674(00)00162-8 · DOI
  4. Brenner, 1974, The genetics of C. elegans., Genetics, 77, 71, 10.1093/genetics/77.1.71 · DOI
  5. Brown, 2009, The JIP3 scaffold protein UNC-16 regulates RAB-5 dependent membrane trafficking at C. elegans synapses., Dev. Neurobiol., 69, 174, 10.1002/dneu.20690 · DOI
  6. Burkhardt, 1997, Overexpression of the dynamitin (p50) subunit of the dynactin complex disrupts dynein-dependent maintenance of membrane organelle distribution., J. Cell Biol., 139, 469, 10.1083/jcb.139.2.469 · DOI
  7. Byrd, 2001, UNC-16, a JNK-signaling scaffold protein, regulates vesicle transport in C. elegans., Neuron, 32, 787, 10.1016/S0896-6273(01)00532-3 · DOI
  8. Charlie, 2006, Presynaptic UNC-31 (CAPS) is required to activate the Gαs pathway of the synaptic signaling network., Genetics, 172, 943, 10.1534/genetics.105.049577 · DOI · Paper page
  9. Charlie, 2006, The dunce cAMP phosphodisterase PDE-4 negatively regulates Gαs-dependent and Gαs-independent cAMP pools in the Caenorhabditis elegans synaptic signaling network., Genetics, 173, 111, 10.1534/genetics.105.054007 · DOI
  10. Chun, 2008, UNC-108/Rab2 Regulates Post-endocytic Trafficking in C. elegans., Mol. Biol. Cell, 19, 2682, 10.1091/mbc.e07-11-1120 · DOI · Paper page
  11. Dejima, 2010, Two Golgi-resident 3′-phosphoadenosine 5′-phosphosulfate transporters play distinct roles in heparan sulfate modifications and embryonic and larval development in Caenorhabditis elegans., J. Biol. Chem., 285, 24717, 10.1074/jbc.M109.088229 · DOI
  12. Duerr, 2001, Identified neurons in C. elegans coexpress vesicular transporters for acetylcholine and monoamines., Am. J. Physiol. Cell Physiol., 280, C1616, 10.1152/ajpcell.2001.280.6.C1616 · DOI
  13. Edwards, 2008, A novel molecular solution for ultraviolet light detection in Caenorhabditis elegans., PLoS Biol., 6, e198, 10.1371/journal.pbio.0060198 · DOI
  14. Edwards, 2009, Impaired dense core vesicle maturation in Caenorhabditis elegans mutants lacking Rab2., J. Cell Biol., 186, 881, 10.1083/jcb.200902095 · DOI · Paper page
  15. Esposito, 2007, Efficient and cell specific knock-down of gene function in targeted C. elegans neurons., Gene, 395, 170, 10.1016/j.gene.2007.03.002 · DOI
  16. Grill, 2007, C. elegans RPM-1 regulates axon termination and synaptogenesis through the Rab GEF GLO-4 and the Rab GTPase GLO-1., Neuron, 55, 587, 10.1016/j.neuron.2007.07.009 · DOI
  17. Grosshans, 2006, Rabs and their effectors: achieving specificity in membrane traffic., Proc. Natl. Acad. Sci. USA, 103, 11821, 10.1073/pnas.0601617103 · DOI · Paper page
  18. Grubb, 2010, Building and maintaining the axon initial segment., Curr. Opin. Neurobiol., 20, 481, 10.1016/j.conb.2010.04.012 · DOI
  19. Hall, 1991, Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans., Cell, 65, 837, 10.1016/0092-8674(91)90391-B · DOI
  20. Hamill, 2002, Centrosome maturation and mitotic spindle assembly in C. elegans require SPD-5, a protein with multiple coiled-coil domains., Dev. Cell, 3, 673, 10.1016/S1534-5807(02)00327-1 · DOI
  21. Ito, 1999, JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway., Mol. Cell. Biol., 19, 7539, 10.1128/MCB.19.11.7539 · DOI · Paper page
  22. Kalatzis, 2001, Cystinosin, the protein defective in cystinosis, is a H(+)-driven lysosomal cystine transporter., EMBO J., 20, 5940, 10.1093/emboj/20.21.5940 · DOI
  23. Kapust, 2001, Tobacco etch virus protease: mechanism of autolysis and rational design of stable mutants with wild-type catalytic proficiency., Protein Eng., 14, 993, 10.1093/protein/14.12.993 · DOI
  24. Kelkar, 2005, Role of the JIP4 scaffold protein in the regulation of mitogen-activated protein kinase signaling pathways., Mol. Cell. Biol., 25, 2733, 10.1128/MCB.25.7.2733-2743.2005 · DOI · Paper page
  25. Koushika, 2004, Mutations in Caenorhabditis elegans cytoplasmic dynein components reveal specificity of neuronal retrograde cargo., J. Neurosci., 24, 3907, 10.1523/JNEUROSCI.5039-03.2004 · DOI
  26. Mangahas, 2008, The small GTPase Rab2 functions in the removal of apoptotic cells in Caenorhabditis elegans., J. Cell Biol., 180, 357, 10.1083/jcb.200708130 · DOI
  27. Maxfield, 2004, Endocytic recycling., Nat. Rev. Mol. Cell Biol., 5, 121, 10.1038/nrm1315 · DOI · Paper page
  28. Mello, 1991, Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequences., EMBO J., 10, 3959, 10.1002/j.1460-2075.1991.tb04966.x · DOI
  29. Miller, 1999, Goα and diacylglycerol kinase negatively regulate the Gqα pathway in C. elegans., Neuron, 24, 323, 10.1016/S0896-6273(00)80847-8 · DOI
  30. Montagnac, 2009, ARF6 Interacts with JIP4 to control a motor switch mechanism regulating endosome traffic in cytokinesis., Curr. Biol., 19, 184, 10.1016/j.cub.2008.12.043 · DOI · Paper page
  31. Nguyen, 2005, JLP associates with kinesin light chain 1 through a novel leucine zipper-like domain., J. Biol. Chem., 280, 30185, 10.1074/jbc.M505499200 · DOI · Paper page
  32. Okada, 1995, The neuron-specific kinesin superfamily protein KIF1A is a unique monomeric motor for anterograde axonal transport of synaptic vesicle precursors., Cell, 81, 769, 10.1016/0092-8674(95)90538-3 · DOI
  33. Orci, 2000, Exclusion of Golgi residents from transport vesicles budding from Golgi cisternae in intact cells., J. Cell Biol., 150, 1263, 10.1083/jcb.150.6.1263 · DOI
  34. Pack-Chung, 2007, A Drosophila kinesin required for synaptic bouton formation and synaptic vesicle transport., Nat. Neurosci., 10, 980, 10.1038/nn1936 · DOI
  35. Patel, 1993, Cloning by insertional mutagenesis of a cDNA encoding Caenorhabditis elegans kinesin heavy chain., Proc. Natl. Acad. Sci. USA, 90, 9181, 10.1073/pnas.90.19.9181 · DOI · Paper page
  36. Perez-Mansilla, 2009, A network of G-protein signaling pathways control neuronal activity in C. elegans., Adv. Genet., 65, 145, 10.1016/S0065-2660(09)65004-5 · DOI
  37. Prekeris, 1998, Syntaxin 13 mediates cycling of plasma membrane proteins via tubulovesicular recycling endosomes., J. Cell Biol., 143, 957, 10.1083/jcb.143.4.957 · DOI · Paper page
  38. Reynolds, 2005, Convergent, RIC-8 dependent Gα signaling pathways in the C. elegans synaptic signaling network., Genetics, 169, 650, 10.1534/genetics.104.031286 · DOI
  39. Rolls, 2002, Targeting of rough endoplasmic reticulum membrane proteins and ribosomes in invertebrate neurons., Mol. Biol. Cell, 13, 1778, 10.1091/mbc.01-10-0514 · DOI
  40. Rostaing, 2004, Preservation of immunoreactivity and fine structure of adult C. elegans tissues using high-pressure freezing., J. Histochem. Cytochem., 52, 1, 10.1177/002215540405200101 · DOI
  41. Sakaguchi, 2004, Roles of MAP kinase cascades in Caenorhabditis elegans., J. Biochem., 136, 7, 10.1093/jb/mvh097 · DOI
  42. Sakamoto, 2005, The Caenorhabditis elegans UNC-14 RUN domain protein binds to the kinesin-1 and UNC-16 complex and regulates synaptic vesicle localization., Mol. Biol. Cell, 16, 483, 10.1091/mbc.e04-07-0553 · DOI
  43. Schade, 2005, Mutations that rescue the paralysis of C. elegans ric-8 (Synembryn) mutants activate the Gαs pathway and define a third major branch of the synaptic signaling network., Genetics, 169, 631, 10.1534/genetics.104.032334 · DOI
  44. Sieburth, 2005, Systematic analysis of genes required for synapse structure and function., Nature, 436, 510, 10.1038/nature03809 · DOI
  45. Song, 2009, A selective filter for cytoplasmic transport at the axon initial segment., Cell, 136, 1148, 10.1016/j.cell.2009.01.016 · DOI · Paper page
  46. Sumakovic, 2009, UNC-108/RAB-2 and its effector RIC-19 are involved in dense core vesicle maturation in Caenorhabditis elegans., J. Cell Biol., 186, 897, 10.1083/jcb.200902096 · DOI · Paper page
  47. Sun, 2011, Sunday Driver/JIP3 binds kinesin heavy chain directly and enhances its motility., EMBO J. 30: 3416–3429., 10.1038/emboj.2011.229 · DOI
  48. Verhey, 2001, Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules., J. Cell Biol., 152, 959, 10.1083/jcb.152.5.959 · DOI · Paper page
  49. Watanabe, 2011, Protein localization in electron micrographs using fluorescence nanoscopy., Nat. Methods, 8, 80, 10.1038/nmeth.1537 · DOI
  50. Weimer, 2005, Synaptic vesicle docking: a putative role for the Munc18/Sec1 protein family., Curr. Top. Dev. Biol., 65, 83, 10.1016/S0070-2153(04)65003-4 · DOI
  51. Williams, 2007, Trio’s Rho-specific GEF domain is the missing Gαq effector in C. elegans., Genes Dev., 21, 2731, 10.1101/gad.1592007 · DOI
  52. Winckler, 1999, A diffusion barrier maintains distribution of membrane proteins in polarized neurons., Nature, 397, 698, 10.1038/17806 · DOI
  53. Yang, 2005, Kinesin-1 mediates translocation of the meiotic spindle to the oocyte cortex through KCA-1, a novel cargo adapter., J. Cell Biol., 169, 447, 10.1083/jcb.200411132 · DOI

Cited by

Sorted by citations

Metadata

Authors
Edwards, S. L., Yu, S.-C., Hoover, C. M., Phillips, B. C., Richmond, J. E., & Miller, K. G.
Affiliations
  • Genetic Models of Disease Program , Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104
  • Department of Biological Sciences , University of Illinois at Chicago, Illinois 60607
Venue
Genetics
Publisher
Oxford University Press (OUP)
Published
2013-05-01
Volume
194
Issue
1
Pages
143-161
ISSN
1943-2631
DOI
10.1534/genetics.112.147348
Cited by
76
References
3
Language
en
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review