Collybistin

Collybistin is a brain specific^[1] protein identified as a regulator of the localization of gephyrin, inducing the formation of submembrane gephyrin aggregates that accumulate glycine and GABA receptors. In 2000 it was identified as a gephyrin binding partner, and an important determinant of inhibitory postsynaptic membrane formation and plasticity.^[1] Gephyrin and collybistin are recruited to developing postsynaptic membranes of inhibitory synapses by the trans-synaptic adhesion molecule neuroligin-2,^[2] where they provide the scaffold for the clustering of inhibitory postsynaptic receptors to form a functioning inhibitory synapse.

Isoforms

The gene ARHGEF9 (aka ARHDH) codes for Collybistin. There are currently 3 known isoforms of Collybistin. Each isoform is similar in that they contain a RhoGEF binding (DH) domain, and a pleckstrin homology (PH) domain.^[3] Where they differ is at the N-terminus in both sequence and whether or not a Src-homology (SH3) domain will be present. They also differ in the C-terminus sequence. The isoforms are referred to as CB1, CB2, and CB3. These three forms have been identified in rats, while only CB3 has been identified in humans and is referred to as hPEM2.^[4]

References

^ ^a ^b Betz, Heinrich; Kins, Stefan; Kirsch, Joachim (2000). "Collybistin, a newly identified brain-specific GEF, induces submembrane clustering of gephyrin". Nature Neuroscience. 3 (1): 22–9. doi:10.1038/71096. PMID 10607391.
^ Poulopoulos, Alexandros; Aramuni, Gayane; Meyer, Guido; Soykan, Tolga; Hoon, Mrinalini; Papadopoulos, Theofilos; Zhang, Mingyue; Paarmann, Ingo; et al. (2009). "Neuroligin 2 Drives Postsynaptic Assembly at Perisomatic Inhibitory Synapses through Gephyrin and Collybistin". Neuron. 63 (5): 628–42. doi:10.1016/j.neuron.2009.08.023. PMID 19755106.
^ Miler, Megan; Yan, Yan; Eipper, Betty; Mains, Richard (2013). "Neuronal Rho GEFs in Synaptic Physiology and Behavior". The Neuroscientist. 19 (2): 255–273. doi:10.1177/1073858413475486. PMC 3927235. PMID 23401188.
^ Fritschy, Jean-Marc; Panzanelli, Patrizia; Tyagarjan, Shiva (2012). "Molecular and functional heterogeneity of GABAergic synapses" (PDF). Cellular and Molecular Life Sciences. 69 (15): 2485–99. doi:10.1007/s00018-012-0926-4. PMID 22314501.

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[:0-1] Betz, Heinrich; Kins, Stefan; Kirsch, Joachim (2000). "Collybistin, a newly identified brain-specific GEF, induces submembrane clustering of gephyrin". Nature Neuroscience. 3 (1): 22–9. doi:10.1038/71096. PMID 10607391.

[2] Poulopoulos, Alexandros; Aramuni, Gayane; Meyer, Guido; Soykan, Tolga; Hoon, Mrinalini; Papadopoulos, Theofilos; Zhang, Mingyue; Paarmann, Ingo; et al. (2009). "Neuroligin 2 Drives Postsynaptic Assembly at Perisomatic Inhibitory Synapses through Gephyrin and Collybistin". Neuron. 63 (5): 628–42. doi:10.1016/j.neuron.2009.08.023. PMID 19755106.

[3] Miler, Megan; Yan, Yan; Eipper, Betty; Mains, Richard (2013). "Neuronal Rho GEFs in Synaptic Physiology and Behavior". The Neuroscientist. 19 (2): 255–273. doi:10.1177/1073858413475486. PMC 3927235. PMID 23401188.

[4] Fritschy, Jean-Marc; Panzanelli, Patrizia; Tyagarjan, Shiva (2012). "Molecular and functional heterogeneity of GABAergic synapses" (PDF). Cellular and Molecular Life Sciences. 69 (15): 2485–99. doi:10.1007/s00018-012-0926-4. PMID 22314501.

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