Article
- The EMBO Journal (2007) 26, 1761 - 1771
- doi:10.1038/sj.emboj.7601625
Published online: 8 March 2007
Subject Category:
Post-phosphorylation prolyl isomerisation of gephyrin represents a mechanism to modulate glycine receptors function
M Moretto Zita1, Ivan Marchionni1, Elisa Bottos1, Massimo Righi1, Giannino Del Sal2,3, Enrico Cherubini1 and Paola Zacchi1
- International School for Advanced Studies, Neuroscience Programme, Area Science Park, Trieste, Italy
- Laboratorio Nazionale CIB, AREA Science Park, Trieste, Italy
- Dipartimento di Biochimica Biofisica Chimica delle Macromolecole, Trieste, Italy
Correspondence to:
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
Abstract
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.
Keywords:
- gephyrin,
- glycine inhibitory receptors,
- Pin1,
- proline directed phosphorylation
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