Universität zu Köln

Burdina, Nele ORCID: 0009-0000-3200-918X, Liebsch, Filip ORCID: 0000-0002-0955-8065, Macha, Arthur ORCID: 0009-0007-1798-4412, Gil, Joaquín Lucas Ortuño, Frommelt, Pia, Rais, Irina ORCID: 0000-0002-0367-1980, Basler, Fabian ORCID: 0000-0001-8999-2568, Pöpsel, Simon ORCID: 0000-0002-8304-4062 and Schwarz, Guenter ORCID: 0000-0002-2118-9338 (2025). Phosphoinositide‐ and Collybistin‐Dependent Synaptic Clustering of Gephyrin. Journal of Neurochemistry, 169 (8). pp. 1-19. Wiley. ISSN 0022-3042

PDF Journal of Neurochemistry - 2025 - Burdina - Phosphoinositide‐ and Collybistin‐Dependent Synaptic Clustering of Gephyrin.pdf Bereitstellung unter der CC-Lizenz: Creative Commons Attribution. Download (7MB)

Abstract

Gephyrin is the main scaffolding protein at inhibitory synapses, clustering glycine and GABAA receptors. At specific GABAergic synapses, the nucleotide exchange factor collybistin recruits gephyrin to the postsynaptic membrane via interaction with phosphoinositides. However, the molecular mechanisms underlying the formation, maintenance, and regulation of collybistin-dependent gephyrin clusters remain poorly understood. This study sheds light on the molecular mechanism of gephyrin cluster formation on the basis of gephyrin self-oligomerization induced by collybistin, leading to the formation of a high-molecular weight (> 5 MDa) gephyrin-collybistin complex, which is regulated in two ways: First, plasma-membrane phosphoinositides promote complex formation, demonstrating their critical role in membrane targeting and stabilization of gephyrin-collybistin clusters at postsynaptic sites. Second, gephyrin phosphorylation at Ser325 abolishes complex formation with collybistin, thus impairing collybistin-dependent gephyrin clustering at GABAergic synapses. Collectively, our data demonstrate a molecular mechanism for synaptic clustering of gephyrin, which involves collybistin- and phosphoinositide-dependent formation of high-molecular weight gephyrin oligomers.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Burdina, Nele UNSPECIFIED https://orcid.org/0009-0000-3200-918X UNSPECIFIED Liebsch, Filip UNSPECIFIED https://orcid.org/0000-0002-0955-8065 UNSPECIFIED Macha, Arthur UNSPECIFIED https://orcid.org/0009-0007-1798-4412 UNSPECIFIED Gil, Joaquín Lucas Ortuño UNSPECIFIED UNSPECIFIED UNSPECIFIED Frommelt, Pia UNSPECIFIED UNSPECIFIED UNSPECIFIED Rais, Irina UNSPECIFIED https://orcid.org/0000-0002-0367-1980 UNSPECIFIED Basler, Fabian UNSPECIFIED https://orcid.org/0000-0001-8999-2568 UNSPECIFIED Pöpsel, Simon UNSPECIFIED https://orcid.org/0000-0002-8304-4062 UNSPECIFIED Schwarz, Guenter UNSPECIFIED https://orcid.org/0000-0002-2118-9338 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-806470
Identification Number:	10.1111/jnc.70169
Journal or Publication Title:	Journal of Neurochemistry
Volume:	169
Number:	8
Page Range:	pp. 1-19
Number of Pages:	19
Date:	8 August 2025
Publisher:	Wiley
ISSN:	0022-3042
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences Faculty of Medicine
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry Zentrum für Molekulare Medizin
Subjects:	Life sciences Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language collybistin ; GABA receptors ; gephyrin ; inhibitory synapse ; phosphoinositides ; synaptic clustering English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/80647