Collybistin, a newly identified brain-specific GEF, induces submembrane clustering of gephyrin

The formation of postsynaptic GABA(A) and glycine receptor clusters require s the receptor-associated peripheral membrane protein gephyrin. Here we des cribe two splice variants of a novel gephyrin-binding protein, termed colly bistin I and II, which belong to the family of dbl-like GDP/GTP exchange fa ctors (GEFs). Co-expression of collybistin II with gephyrin induced the for mation of submembrane gephyrin aggregates that accumulate hetero-oligomeric glycine receptors. Our data suggest that collybistin II regulates the memb rane deposition of gephyrin by activating a GTPase of the Rho/Rac family. T herefore, this protein may be an important determinant of inhibitory postsy naptic membrane formation and plasticity.