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PMID: 8022809 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Interaction of Grb2 via its Src homology 3 domains with synaptic proteins including synapsin I.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 14 ·1994-07-05 ·Pages 6486-90

McPherson PS, Czernik AJ, Chilcote TJ, Onofri F, Benfenati F, Greengard P, Schlessinger J, De Camilli P

Abstract

Grb2 is a 25-kDa adaptor protein composed of a Src homology 2 (SH2) domain and two flanking Src homology 3 (SH3) domains. One function of Grb2 is to couple tyrosine-phosphorylated proteins (through its SH2 domain) to downstream effectors (through its SH3 domains). Using an overlay assay, we have identified four major Grb2-binding proteins in synaptic fractions. These proteins interact with wild-type Grb2 but not with Grb2 containing point mutations in each of its two SH3 domains corresponding to the loss of function mutants in the Caenorhabditis elegans Grb2 homologue sem-5. Two of the proteins, mSos and dynamin, were previously shown to bind Grb2. The third protein of 145 kDa is brain specific and to our knowledge has not been previously described. The fourth protein is synapsin I. Dynamin is required for synaptic vesicle endocytosis and synapsin I is thought to mediate the interaction of synaptic vesicles with the presynaptic cytomatrix. These data suggest that Grb2, or other proteins containing SH3 domains, may play a role in the regulation of the exo/endocytotic cycle of synaptic vesicles and therefore of neurotransmitter release.

MeSH Terms
Adaptor Proteins, Signal Transducing Animals Brain/metabolism Cerebellum/metabolism DNA Primers Electrophoresis, Polyacrylamide Gel ErbB Receptors/metabolism GRB2 Adaptor Protein Humans Molecular Weight Polymerase Chain Reaction Protein Binding Protein Biosynthesis Proteins/isolation & purification,metabolism Rats Recombinant Fusion Proteins/biosynthesis,isolation & purification,metabolism Sequence Homology, Amino Acid Synapsins/isolation & purification,metabolism Synaptic Vesicles/metabolism
Chemicals
Adaptor Proteins, Signal Transducing DNA Primers GRB2 Adaptor Protein GRB2 protein, human Grb2 protein, rat Proteins Recombinant Fusion Proteins Synapsins ErbB Receptors
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
McPherson P S
Department of Cell Biology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06536.
Czernik A J
Chilcote T J
Onofri F
Benfenati F
Greengard P
Schlessinger J
De Camilli P
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.14.6486
Published
1994-07-05
Pages
6486-90
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC44227
Subset
IM
Grants
NIMH NIH HHS · MH 39327 · United States
NIMH NIH HHS · MH 54596 · United States
External Links
PubMed source DOI: 10.1073/pnas.91.14.6486 PMC Full Text View journal details
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