Collybistin, a newly identified brain-specific GEF, induces submembrane clustering of gephyrin.
The formation of postsynaptic GABAA and glycine receptor clusters requires the receptor-associated peripheral membrane protein gephyrin. Here we describe two splice variants of a novel gephyrin-binding protein, termed collybistin I and II, which belong to the family of dbl-like GDP/GTP exchange factors (GEFs). Co-expression of collybistin II with gephyrin induced the formation of submembrane gephyrin aggregates that accumulate hetero-oligomeric glycine receptors. Our data suggest that collybistin II regulates the membrane deposition of gephyrin by activating a GTPase of the Rho/Rac family. Therefore, this protein may be an important determinant of inhibitory postsynaptic membrane formation and plasticity.
Kins
S
S
Department of Neurochemistry, Max-Planck-Institute for Brain Research, Deutschordenstr. 46, D-60528 Frankfurt, Germany.
Betz
H
H
Kirsch
J
J
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D017124:Conserved Sequence; D020558:GTP Phosphohydrolases / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D020033:Protein Isoforms / Q000378:metabolism / Q000502:physiology; D051381:Rats; D018009:Receptors, Glycine / Q000378:metabolism; D064067:Rho Guanine Nucleotide Exchange Factors; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism*; D018909:src Homology Domains
C577410:ARHGEF9 protein, human; C577404:Arhgef9 protein, rat; D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D046911:Macromolecular Substances; D008565:Membrane Proteins; D020033:Protein Isoforms; D018009:Receptors, Glycine; D064067:Rho Guanine Nucleotide Exchange Factors; C073441:gephyrin; D020558:GTP Phosphohydrolases