Post-phosphorylation prolyl isomerisation of gephyrin represents a mechanism to modulate glycine receptors function |
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| Authors: | Zita M Moretto Marchionni Ivan Bottos Elisa Righi Massimo Del Sal Giannino Cherubini Enrico Zacchi Paola |
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| Affiliation: | International School for Advanced Studies, Neuroscience Programme, Area Science Park, Basovissa SS14, 34012 Trieste, Italy. |
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| 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. |
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