The GDP-GTP Exchange Factor Collybistin: An Essential Determinant of Neuronal Gephyrin Clustering

• DOI: 10.1523/jneurosci.1184-04.2004
• Publication Date: 2004-06-23T18:38:21Z
• Authors: Kirsten Harvey; Ian C. Duguid; Melissa J. Alldred; Sarah E. Beatty; Hamish Ward; Nicholas H. Keep; Sue E. Lingenfelter; Brian R. Pearce; Johan Lundgren; Michael J. Owen; Trevor G. Smart; Bernhard Lüscher; Mark I. Rees; Robert J. Harvey
• Keywords: Gephyrin; Pleckstrin homology domain

Glycine receptors (GlyRs) and specific subtypes of GABA A are clustered at synapses by the multidomain protein gephyrin, which in turn is translocated to cell membrane GDP-GTP exchange factor collybistin. We report characterization several new variants collybistin, created alternative splicing exons encoding an N-terminal src homology 3 (SH3) domain three alternate C termini (CB1, CB2, CB3). The presence SH3 negatively regulates ability collybistin translocate gephyrin submembrane microaggregates transfected mammalian cells. Because majority native isoforms appear harbor domain, this suggests that activity may be regulated protein-protein interactions domain. localized binding sites for GlyR β subunit C-terminal MoeA show multimerization required collybistin-gephyrin GlyR-gephyrin interactions. also demonstrate clustering recombinant systems cultured neurons requires both intact pleckstrin vital importance inhibitory synaptogenesis underlined discovery a mutation (G55A) exon 2 human gene ( ARHGEF9 ) patient with clinical symptoms hyperekplexia epilepsy. manifestation missense result, least part, from mislocalization major receptor subtype.