Gephyrin: a Key Regulatory Protein of Inhibitory Synapses and Beyond

Overview

Journal Histochem Cell Biol

Publisher Springer

Specialties Biochemistry
Cell Biology

Date 2018 Sep 29

PMID 30264265

Citations 32

Authors

Femke L Groeneweg

Christa Trattnig

Jochen Kuhse

Ralph A Nawrotzki

Joachim Kirsch

Affiliations

Soon will be listed here.

Abstract

Scaffolding proteins underlying postsynaptic membrane specializations are important structural and functional components of both excitatory and inhibitory synapses. At inhibitory synapses, gephyrin was identified as anchoring protein. Gephyrin self-assembles into a complex flat submembranous lattice that slows the lateral mobility of glycine and GABA receptors, thus allowing for their clustering at postsynaptic sites. The structure and stability of the gephyrin lattice is dynamically regulated by posttranslational modifications and interactions with binding partners. As gephyrin is the core scaffolding protein for virtually all inhibitory synapses, any changes in the structure or stability of its lattice can profoundly change the packing density of inhibitory receptors and, therefore, alter inhibitory drive. Intriguingly, gephyrin plays a completely independent role in non-neuronal cells, where it facilitates two steps in the biosynthesis of the molybdenum cofactor. In this review, we provide an overview of the role of gephyrin at inhibitory synapses and beyond. We discuss its dynamic regulation, the nanoscale architecture of its synaptic lattice, and the implications of gephyrin dysfunction for neuropathologic conditions, such as Alzheimer's disease and epilepsy.

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