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Cited by 142Neuroscience and Neuropharmacology ResearchProtein Kinase Regulation and GTPase SignalingGenetics and Neurodevelopmental Disorders

The Rho-Specific GEF Lfc Interacts with Neurabin and Spinophilin to Regulate Dendritic Spine Morphology

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Ryan, Xiaozhou P., Alldritt, Jacqueline, Svenningsson, Per, Allen, Patrick B., Wu, Gang-Yi, Nairn, Angus C., Greengard, Paul·2005·Neuron
DOI 10.1016/j.neuron.2005.05.013
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Abstract

Neurabin and spinophilin are homologous protein phosphatase 1 and actin binding proteins that regulate dendritic spine function. A yeast two-hybrid analysis using the coiled-coil domain of neurabin revealed an interaction with Lfc, a Rho GEF. Lfc was highly expressed in brain, where it interacted with either neurabin or spinophilin. In neurons, Lfc was largely found in the shaft of dendrites in association with microtubules but translocated to spines upon neuronal stimulation. Moreover, expression of Lfc resulted in reduction in spine length and size. Both the translocation and the effect on spine morphology depended on the coiled-coil domain of Lfc. Coexpression of neurabin or spinophilin with Lfc resulted in their clustering together with F-actin, a process that depended on Rho activity. Thus, interaction between Lfc and neurabin/spinophilin selectively regulates Rho-dependent organization of F-actin in spines and is a link between the microtubule and F-actin cytoskeletons in dendrites.

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  • A previous study showed that GFP-GEF-H1 was localized in the dendritic shaft and translocated to spines only after KCl-dependent depolarization or electrical stimulation.

    “A previous study of GEF-H1 in neurons showed that GFPGEF-H1 was localized in the dendritic shaft and translocated to spines only after KCl-dependent depolarization or electrical stimulation (26).”

    From AMPA receptor and GEF-H1/Lfc complex regulates dendritic spine development through RhoA signaling cascade (2009) · cites this paper as [26]

    The Results (page unavailable) report that GFP-Lfc was mainly in dendritic shafts and moved into spines after KCl depolarization or electrical stimulation; the Discussion identifies human Lfc as GEF-H1. But “only after” is too restrictive: the Results also report translocation after glutamate or NMDA stimulation, and some unstimulated neurons already had Lfc staining in spines. (LLM, conf=0.91)

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  • The previous study used rat GEF-H1 cDNA (encode 958 aa) that is shorter than our rat GEF-H1 cDNA (encode 985 aa).

    “In addition, the previous study (26) used rat GEF-H1 cDNA (encode 958 aa) that is shorter than our rat GEF-H1cDNA(encode985aa).”

    From AMPA receptor and GEF-H1/Lfc complex regulates dendritic spine development through RhoA signaling cascade (2009) · cites this paper as [26]

    The Results section (page unavailable) says the study used rat Lfc and describes probes and antibodies targeting amino acids 701–958 of the full-length protein. This supports the attribution of a rat Lfc/GEF-H1 construct extending to residue 958, but the source does not state the length of the citing authors’ 985-amino-acid cDNA or make that comparison. (LLM, conf=0.78)

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Authors
Ryan, X. P., Alldritt, J., Svenningsson, P., Allen, P. B., Wu, G.-Y., Nairn, A. C., & Greengard, P.
Affiliations
  • Rockefeller University (US)
  • Baylor College of Medicine (US)
  • Yale University (US)
Corresponding author
  • Wu, Gang-Yi
  • Nairn, Angus C.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2005-07
Volume
47
Issue
1
Pages
85-100
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2005.05.013
OpenAlex
W2024378715
Cited by
142
References
6
Citations by year
2026: 2 · 2025: 2 · 2024: 3 · 2023: 2 · 2021: 6 · 2020: 4 · 2019: 1 · 2018: 6 · 2017: 4 · 2016: 12 · 2015: 4 · 2014: 11 · 2013: 6 · 2012: 11
FWCI
4.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Public Health Service (DA10044, DA17919, MH40899)
  • U.S. Army (W81XWH-04-1-0260)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
spinophilin, dendritic spine morphology, Rho GTPase signaling, F-actin organization, microtubule cytoskeleton, coiled-coil domain, neurostimulation, protein-protein interaction, actin-binding proteins, protein phosphatase 1
MeSH terms
Neurabins, Actins, Animals, Brain Chemistry, Carbocyanines, Dendrites, Coloring Agents, Guanosine Diphosphate, Guanosine Triphosphate, Hippocampus, Immunohistochemistry, Microfilament Proteins, Microtubules, Nerve Tissue Proteins, Phalloidine, Transfection, DNA, Complementary, Microscopy, Confocal, Guanine Nucleotide Exchange Factors, Rats

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