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

Nature Neuroscience volume 3, pages 22–29 (2000)Cite this article

Abstract

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.

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Figure 1: Primary structures of rat and human collybistin.
Figure 2: Domain comparison of collybistin and other members of the GEF family.
Figure 3: Collybistin mRNAs are mainly expressed in brain.
Figure 4: Distribution of collybistin and gephyrin mRNAs in the adult rat brain.
Figure 5: Western blot of recombinant collybistin and co-immunoprecipitation of recombinant gephyrin with collybistin.
Figure 6: Co-expression of gephyrin alters the distribution of collybistin I and II in HEK 293 cells.
Figure 7: Collybistin II/gephyrin co-aggregates recruit hetero-oligomeric but not homo-oligomeric GlyRs.

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Acknowledgements

The authors thank Maria Fischer for the construction of the bait vector, Ina Bartnik for technical assistance with in-situ hybridizations and immunocytochemistry and M. Baier and H. Reitz for help in preparing the manuscript. Expression vectors encoding BS69 and the netrin receptor were gifts from R. Bernards and M. Tessier-Lavigne, respectively. This study was supported by Deutsche Forschungsgemeinschaft (Ki339/7-1, SFB 474-B7 (JK), and Ki339/9-1), Stifterverband für die Deutsche Wissenschaft, BMBF (01KV9539/3) and Fonds der Chemischen Industrie.

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  1. Stefan Kins

    Present address: Department of Psychiatric Research, University of Zürich, August-Forel-Str. 7, CH-8008, Zürich, Switzerland

Authors and Affiliations

  1. Department of Neurochemistry, Max-Planck-Institute for Brain Research, Deutschordenstr. 46, Frankfurt, D-60528 , Germany

    Stefan Kins, Heinrich Betz & Joachim Kirsch

  2. Department of Anatomy and Cellular Neurobiology, University of Ulm, Albert-Einstein-Allee 11, Ulm, D-89069, Germany

    Joachim Kirsch

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Correspondence to Heinrich Betz.

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Kins, S., Betz, H. & Kirsch, J. Collybistin, a newly identified brain-specific GEF, induces submembrane clustering of gephyrin. Nat Neurosci 3, 22–29 (2000). https://doi.org/10.1038/71096

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