Universität zu Köln

Falk, Nathalie, Joachimsthaler, Anneka, Kessler, Kristin, Lux, Uwe Thorsten, Noegel, Angelika Anna, Kremers, Jan, Brandstaetter, Johann Helmut and Giessl, Andreas ORCID: 0000-0002-9768-2049 (2019). Lack of a Retinal Phenotype in a Syne-2/Nesprin-2 Knockout Mouse Model. Cells, 8 (10). BASEL: MDPI. ISSN 2073-4409

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Abstract

Syne-2 (also known as Nesprin-2) is a member of a family of proteins that are found primarily in the outer nuclear membrane, as well as other subcellular compartments. Syne-2 contains a C-terminal KASH transmembrane domain and is part of a protein network that associates the nuclear envelope to the cytoskeleton via the binding to actin filaments. Syne-2 plays a role in nuclear migration, nuclear positioning during retinal development, and in ciliogenesis. In a previous study, we showed a connection between Syne-2 and the multifunctional scaffold protein Pericentrin (Pcnt). The elimination of the interaction of Syne-2 and Pcnt showed defects in nuclear migration and the formation of outer segments during retinal development, as well as disturbances in centrosomal migration at the beginning of ciliogenesis in general. In this study, the Syne-2 KO mouse model Nesprin-2oABD (Syne-2(tm1Ngl), MGI) with special attention to Pcnt and ciliogenesis was analyzed. We show reduced expression of Syne-2 in the retina of the Syne-2 KO mouse but found no significant structural-and only a minor functional-phenotype. For the first time, detailed expression analyses showed an expression of a Syne-2 protein larger than 400 kDa (similar to 750 kDa) in the Syne-2/Nesprin-2 KO mouse. In conclusion, the lack of an overt phenotype in Syne-2/Nesprin-2 KO mice suggests the usage of alternative translational start sites, producing Syne-2 splice variants with an intact Pcnt interaction site. Nevertheless, deletion of the actin-binding site in the Syne-2/Nesprin-2 KO mouse revealed a high variability in scotopic oscillatory potentials assuming a novel function of Syne-2 in synchronizing inner retinal processes.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Falk, Nathalie UNSPECIFIED UNSPECIFIED UNSPECIFIED Joachimsthaler, Anneka UNSPECIFIED UNSPECIFIED UNSPECIFIED Kessler, Kristin UNSPECIFIED UNSPECIFIED UNSPECIFIED Lux, Uwe Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Noegel, Angelika Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Kremers, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Brandstaetter, Johann Helmut UNSPECIFIED UNSPECIFIED UNSPECIFIED Giessl, Andreas UNSPECIFIED orcid.org/0000-0002-9768-2049 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-131914
DOI:	10.3390/cells8101238
Journal or Publication Title:	Cells
Volume:	8
Number:	10
Date:	2019
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2073-4409
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NUCLEAR MIGRATION; PERICENTRIN; PROTEINS; CILIA Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13191