The structural biologist was the first to solve the crystal structures of two different artemisinin derivatives artesunate and artemether in a complex with
gephyrin. By binding to inhibitory glycine and GABAA receptors,
gephyrin acts as a central scaffold protein of inhibitory postsynapses in the mammalian central nervous system.
Consistent with this computational prediction, immunohistological analyses revealed significantly decreased numbers of [GABA.sub.A] receptor and
gephyrin clusters in the granule cell layer of NL2 KOs, indicating a loss of synaptic [GABA.sub.A] receptors from the somata of granule cells.
(31)
Gephyrin is a major scaffolding molecule of inhibitory postsynaptic specialization.
Very recently, long-term treatment with antimalarial drugs that target
gephyrin (a protein that participates in GABAA-R transport to the membrane), or treatment with GABA, was shown to promote islet [alpha]-cell transdifferentiation into [beta]-cells [22, 23].
In transgenic (TG2576) and Swedish transgenic (TG-SwDI) mice, dihydromyricetin may reduce A[beta] peptide production and restore
gephyrin levels, GABAergic transmission, and functional synapses, leading to improvement of clinical symptoms [63].
Burkarth N, Kriebel M, Kranz EU, Volkmer H, 2007, Neurofascin regulates the formation of
gephyrin clusters and their subsequent translocation to the axon hillock of hippocampal neurons.
Splice-specific Functions of
Gephyrin in Molybdenum Cofactor Biosynthesis, Journal of Biological Chemistry 283 (25): 17370-9.
[39] Antibodies directed against
gephyrin, a post-synaptic cytosolic vesicle protein, may also be produced.
Bechade, "Expression of glycine receptor a subunits and
gephyrin in cultured spinal neurons," European Journal of Neuroscience, vol.
[120] A study by Chhatwal and colleagues, [121] found that
gephyrin (which regulates GABAergic neurotransmission by clustering GABAA receptors at the synapse) is unregulated after extinction training but down-regulated after fear acquisition, confirming the role of GABAA receptors in both fear acquisition and extinction.
Fast and reversible trapping of surface glycine receptors by
gephyrin. Nat Neurosci 2001;4:253-60.
A major inhibitory synaptic receptor is the hetero-pentameric GABAA Receptor (GABAAR), which is stabilised in the synapse by the intracellular scaffolding protein
gephyrin.
Gephyrin, in turn, is recruited to and stabilised at the synapse by the adhesion protein neuroligin-2 (NL2).
