array tomography immunofluorescence of an LRWhite-embedded 70 nm section from adult mouse cortex with L106/4 (green), rabbit mAb GAD2 (Cell Signaling #5843, magenta) and DAPI (blue). The insert shows three consecutive sections through the synapse that is marked with a white box. Image courtesy of Kristina Micheva (Stanford).
In neuronal tissue, gephyrin is a scaffolding protein that self assembles in a complex, flat submembraneous lattice that inhibits mobility of the glycine receptors (GlyR) and GABAA receptors (GABAAR) causing clustering at post synaptic sites (Groeneweg et al, 2018). In non-neuronal tissue gephyrin plays a critical role in the molybdendum cofactor (MoCo) biosynthesis of essential life molybdoenzymes, like sulphite oxidase (Groeneweg et al, 2018). Three functional domains have been identified in gephyrin: the stable, structural G and E domains, and the C domain which is intrinsically unstructured leading to multiple isoforms (108, 105, 102, 98, 90 kDa) (Kawasaki, et al 1997). The 93 kDa protein predominantly expressed in the brain and located in the plasma membrane, has a 10X stronger affinity for the GlyR than the GABAAR. Gephyrin’s flexibility to change its size and molecular density is directly correlated to its high affinity to the GlyR-ß subunit, and is required for anchoring and accurate clustering of GlyRs at post synaptic sites and microtubule transport chains (Greoneweg et al, 2018). A consistent parameter in the pathogenesis of Alzheimers Disease shows a decrease of inhibitory GABAergic synapses and gephyrin, and increased levels of an insoluble 37 kDa gephyrin fragment not detected in healthy, non-AD models (Kiss et al, 2016).
AT, ICC, IHC, WB
GPHN GPH KIAA1385
Fusion protein amino acids 1-181 (N-terminus) of human Gephyrin (also known as Molybdopterin molybdenumtransferase, MPT Mo-transferase, Domain G, Domain E, Putative glycine receptor-tubulin linker protein, GPHN, GPH and KIAA1385, accession number Q9NQX3); Mouse: 100% identity (181/181 amino acids identical); Rat: 100% identity (181/181 amino acids identical) with isoform 5, slightly lower with other isoforms
Human, Mouse, Rat
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