Functional analyses of Pericentrin and Syne-2 interaction in ciliogenesis

Falk, Nathalie; Kessler, Kristin; Schramm, Sinja-Fee; Boldt, Karsten; Becirovic, Elvir; Michalakis, Stylianos; Regus-Leidig, Hanna; Noegel, Angelika A.; Ueffing, Marius; Thiel, Christian T.; Roepman, Ronald; Brandstaetter, Johann Helmut und Giessl, Andreas (2018): Functional analyses of Pericentrin and Syne-2 interaction in ciliogenesis. In: Journal of Cell Science, Bd. 131, Nr. 16

Abstract

Pericentrin (Pcnt) is a multifunctional scaffold protein and mutations in the human PCNT gene are associated with several diseases, including ciliopathies. Pcnt plays a crucial role in ciliary development in olfactory receptor neurons, but its function in the photoreceptorconnecting cilium is unknown. We downregulated Pcnt in the retina ex vivo and in vivo via a virus-based RNA interference approach to study Pcnt function in photoreceptors. ShRNA-mediated knockdown of Pcnt impaired the development of the connecting cilium and the outer segment of photoreceptors, and caused a nuclear migration defect. In protein interaction screens, we found that the outer nuclear membrane protein Syne-2 (also known as Nesprin-2) is an interaction partner of Pcnt in photoreceptors. Syne-2 is important for positioning murine photoreceptor cell nuclei and for centrosomal migration during early ciliogenesis. CRISPR/Cas9mediated knockout of Syne-2 in cell culture led to an overexpression and mislocalization of Pcnt and to ciliogenesis defects. Our findings suggest that the Pcnt-Syne-2 complex is important for ciliogenesis and outer segment formation during retinal development and plays a role in nuclear migration.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department für Pharmazie - Zentrum für Pharmaforschung
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 0021-9533
• Sprache: Englisch