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| Subject Categories: Signal Transduction |
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| The EMBO Journal
(2007) 26, 1761–1771, doi:10.1038/sj.emboj.7601625 Published online 8 March 2007 |
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| Post-phosphorylation prolyl isomerisation of gephyrin represents a mechanism to modulate glycine receptors function |
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| M Moretto Zita1, Ivan Marchionni1, Elisa Bottos1, Massimo Righi1, Giannino Del Sal2, 3, Enrico Cherubini1 and Paola Zacchi1 |
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1 International School for Advanced Studies, Neuroscience Programme, Area Science Park, Trieste, Italy 2 Laboratorio Nazionale CIB, AREA Science Park, Trieste, Italy 3 Dipartimento di Biochimica Biofisica Chimica delle Macromolecole, Trieste, Italy To whom correspondence should be addressed Paola Zacchi, International School for Advanced Studies, Neuroscience Programme, Area Science Park, Basovizza SS14 Km 163.5, 34012 Trieste, Italy. Tel.: +39 403756510; Fax:+39 403756502; E-mail: zacchi@sissa.it Received 4 August 2006; Accepted 31 January 2007; Published online 8 March 2007. |
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| Abstract |
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| The microtubule binding protein gephyrin plays a prominent role in establishing and maintaining a high concentration of inhibitory glycine receptors juxtaposed to presynaptic releasing sites. Here, we show that endogenous gephyrin undergoes proline-directed phosphorylation, which is followed by the recruitment of the peptidyl-prolyl isomerase Pin1. The interaction between gephyrin and Pin1 is strictly dependent on gephyrin phosphorylation and requires serine–proline consensus sites encompassing the gephyrin proline-rich domain. Upon binding, Pin1 triggers conformational changes in the gephyrin molecule, thus enhancing its ability to bind the beta subunit of GlyRs. Consistently, a downregulation of GlyR clusters was detected in hippocampal neurons derived from Pin1 knockout mice, which was paralleled by a reduction in the amplitude of glycine-evoked currents. Our results suggest that phosphorylation-dependent prolyl isomerisation of gephyrin represents a mechanism for regulating GlyRs function. |
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| Keywords: gephyrin, glycine inhibitory receptors, Pin1, proline directed phosphorylation |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSNature Cell Biology News and Views (01 Nov 2002) Getting a bead on receptor movements Nature Neuroscience News and Views (01 Mar 2001) RESEARCHTIRAP: an adapter molecule in the Toll signaling pathway Nature Immunology Article (01 Sep 2001) Structural basis of dynamic glycine receptor clustering by gephyrin The EMBO Journal Article (07 Jul 2004) |
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