Gephyrin: where do we stand, where do we go?
Gephyrin is a multifunctional protein responsible for molybdenum cofactor synthesis and the clustering of glycine and GABA(A) receptors at inhibitory synapses. Based on the structure of its two conserved domains, G and E, gephyrin is thought to form a hexagonal lattice serving as a scaffold for accessory proteins at postsynaptic sites. However, important aspects of gephyrin gene expression, protein structure and regulation, as well as the role of gephyrin in synapse formation and plasticity, remain poorly understood. Here we review the current state of knowledge about gephyrin, highlighting new research avenues based on a different structural model and a revised nomenclature for gephyrin splice variants. Unraveling the biology of gephyrin will further our understanding of glycinergic and GABAergic synapses in health and disease.
Fritschy
Jean-Marc
JM
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. fritschy@pharma.uzh.ch
Harvey
Robert J
RJ
Schwarz
Günter
G
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D017729:Presynaptic Terminals / Q000378:metabolism; D011487:Protein Conformation; D011963:Receptors, GABA-A / Q000378:metabolism; D018009:Receptors, Glycine / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002352:Carrier Proteins; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; C073441:gephyrin; D005680:gamma-Aminobutyric Acid; D005998:Glycine