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          Institute: MPI für medizinische Forschung     Collection: Jahbruch 2014_archival     Display Documents



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ID: 681428.0, MPI für medizinische Forschung / Jahbruch 2014_archival
Collybistin activation by GTP−TC10 enhances
postsynaptic gephyrin clustering and hippocampal
GABAergic neurotransmission
Translation of Title:Collybistin activation by GTP−TC10 enhances
postsynaptic gephyrin clustering and hippocampal
GABAergic neurotransmission
Authors:Mayer, Simone; Kumar, Rohit; Jaiswal, Mamta; Soykan, Tolga; Ahmadian, Mohammad Reza; Brose, Nils; Betz, Heinrich; Rhee, Jeong−Seop; Papadopoulos, Theofilos
Language:English
Date of Publication (YYYY-MM-DD):2013-12-17
Title of Journal:Proceedings of the National Academy of Sciences of the USA
Journal Abbrev.:PNAS
Volume:110
Issue / Number:51
Start Page:20795
End Page:20800
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:In many brain regions, gephyrin and GABAA receptor clustering at developing inhibitory synapses depends on the guanine nucleotide exchange factor collybistin (Cb). The vast majority of Cb splice variants contain an autoinhibitory src homology 3 domain, and several synaptic proteins are known to bind to this SH3 domain and to thereby activate gephyrin clustering. However, many functional GABAergic synapses form independently of the known Cb−activating proteins, indicating that additional Cb activators must exist. Here we show that the small Rho−like GTPase TC10 stimulates Cb−dependent gephyrin clustering by binding in its active, GTP−bound state to the pleckstrin homology domain of Cb. Overexpression of a constitutively active TC10 variant in neurons causes an increase in the density of synaptic gephyrin clusters and mean miniature inhibitory postsynaptic current amplitudes, whereas a dominant negative TC10 variant has opposite effects. The enhancement of Cb−induced gephyrin clustering by GTP−TC10 does not depend on the guanine nucleotide exchange activity of Cb but involves an interaction that resembles reported interactions of other small GTPases with their effectors. Our data indicate that GTP−TC10 activates the major src homology 3 domain−containing Cb variants by relieving autoinhibition and thus define an alternative GTPase−driven signaling pathway in the genesis of inhibitory synapses
Free Keywords:Cdc42, RhoQ, neuroligin, postsynaptic scaffold, synaptogenesis
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:wkaiser
Affiliations:MPI für medizinische Forschung/Abteilung Zellphysiologie
MPI für medizinische Forschung/Abteilung Biomedizinische Optik
Identifiers:LOCALID:7975
URI:http%3A%2F%2Fwww.pnas.org%2Fcontent%2F110%2F51%2F2...
URI:http%3A%2F%2Fwww.pnas.org%2Fcontent%2F110%2F51%2F2...
URI:http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F24297...
DOI:10.1073%2Fpnas.1309078110
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