Functional analyses of Pericentrin and Syne-2 interaction in ciliogenesis

Falk N, Keßler K, Schramm SF, Boldt K, Becirovic E, Michalakis S, Regus-Leidig H, Noegel AA, Ueffing M, Thiel C, Roepman R, Brandstätter JH, Gießl A (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Journal of Cell Science Company of Biologists

Book Volume: 131

Journal Issue: 16

DOI: 10.1242/jcs.218487

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 photoreceptor-connecting 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/Cas9-mediated 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.

Authors with CRIS profile

Nathalie Falk Lehrstuhl für Tierphysiologie Kristin Keßler Lehrstuhl für Tierphysiologie Hanna Regus-Leidig Lehrstuhl für Tierphysiologie Christian Thiel Medizinische Fakultät Johann Helmut Brandstätter Lehrstuhl für Tierphysiologie Andreas Gießl Lehrstuhl für Tierphysiologie

Additional Organisation(s)

Institute of Human Genetics

Involved external institutions

Radboud University Nijmegen NL Netherlands (NL) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Universität zu Köln DE Germany (DE) Eberhard Karls Universität Tübingen DE Germany (DE)

How to cite

APA:

Falk, N., Keßler, K., Schramm, S.-F., Boldt, K., Becirovic, E., Michalakis, S.,... Gießl, A. (2018). Functional analyses of Pericentrin and Syne-2 interaction in ciliogenesis. Journal of Cell Science, 131(16). https://doi.org/10.1242/jcs.218487

MLA:

Falk, Nathalie, et al. "Functional analyses of Pericentrin and Syne-2 interaction in ciliogenesis." Journal of Cell Science 131.16 (2018).

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