RGD Reference Report - The GIT family of proteins forms multimers and associates with the presynaptic cytomatrix protein Piccolo. - Rat Genome Database

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The GIT family of proteins forms multimers and associates with the presynaptic cytomatrix protein Piccolo.

Authors: Kim, S  Ko, J  Shin, H  Lee, JR  Lim, C  Han, JH  Altrock, WD  Garner, CC  Gundelfinger, ED  Premont, RT  Kaang, BK  Kim, E 
Citation: Kim S, etal., J Biol Chem. 2003 Feb 21;278(8):6291-300. Epub 2002 Dec 6.
RGD ID: 9850090
Pubmed: PMID:12473661   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M212287200   (Journal Full-text)

The cytoskeletal matrix assembled at active zones (CAZ) is implicated in defining neurotransmitter release sites. However, little is known about the molecular mechanisms by which the CAZ is organized. Here we report a novel interaction between Piccolo, a core component of the CAZ, and GIT proteins, multidomain signaling integrators with GTPase-activating protein activity for ADP-ribosylation factor small GTPases. A small region (approximately 150 amino acid residues) in Piccolo, which is not conserved in the closely related CAZ protein Bassoon, mediates a direct interaction with the Spa2 homology domain (SHD) domain of GIT1. Piccolo and GIT1 colocalize at synaptic sites in cultured neurons. In brain, Piccolo forms a complex with GIT1 and various GIT-associated proteins, including betaPIX, focal adhesion kinase, liprin-alpha, and paxillin. Point mutations in the SHD of GIT1 differentially interfere with the association of GIT1 with Piccolo, betaPIX, and focal adhesion kinase, suggesting that these proteins bind to the SHD by different mechanisms. Intriguingly, GIT proteins form homo- and heteromultimers through their C-terminal G-protein-coupled receptor kinase-binding domain in a tail-to-tail fashion. This multimerization enables GIT1 to simultaneously interact with multiple SHD-binding proteins including Piccolo and betaPIX. These results suggest that, through their multimerization and interaction with Piccolo, the GIT family proteins are involved in the organization of the CAZ.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  

Objects Annotated

Genes (Rattus norvegicus)
Arhgef7  (Rho guanine nucleotide exchange factor 7)
Git1  (GIT ArfGAP 1)
Grip1  (glutamate receptor interacting protein 1)
Pclo  (piccolo (presynaptic cytomatrix protein))
Ptk2  (protein tyrosine kinase 2)
Pxn  (paxillin)


Additional Information