The microtubule affinity regulating kinase MARK4 promotes axoneme extension during early ciliogenesis.

Kuhns S, Schmidt K, Reymann J, Gilbert D, Neuner A, Hub B, Carvalho R, Wiedemann P, Zentgraf H, Erfle H, Klingmüller U, Boutros M, Pereira G (2013)

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2013

Journal

The Journal of Cell Biology Rockefeller University Press

Book Volume: 200

Pages Range: 505-22

Journal Issue: 4

DOI: 10.1083/jcb.201206013

Abstract

Despite the critical contributions of cilia to embryonic development and human health, key regulators of cilia formation await identification. In this paper, a functional RNA interference-based screen linked 30 novel protein kinases with ciliogenesis. Of them, we have studied the role of the microtubule (MT)-associated protein/MT affinity regulating kinase 4 (MARK4) in depth. MARK4 associated with the basal body and ciliary axoneme in human and murine cell lines. Ultrastructural and functional analyses established that MARK4 kinase activity was required for initiation of axoneme extension. We identified the mother centriolar protein ODF2 as an interaction partner of MARK4 and showed that ODF2 localization to the centriole partially depended on MARK4. Our data indicated that, upon MARK4 or ODF2 knockdown, the ciliary program arrested before the complete removal of the CP110-Cep97 inhibitory complex from the mother centriole, suggesting that these proteins act at this level of axonemal extension. We propose that MARK4 is a critical positive regulator of early steps in ciliogenesis.

Authors with CRIS profile

Daniel Gilbert Lehrstuhl für Medizinische Biotechnologie

Involved external institutions

Molecular Biology of Centrosomes and Cilia group DE Germany (DE) BioQuant, ViroQuant-CellNetworks RNAi Screening Facility DE Germany (DE) DKFZ-ZMBH Alliance, Center for Molecular and Cellular Biology (ZMBH) DE Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Hochschule Mannheim University of Applied Sciences DE Germany (DE) Ruprecht-Karls-Universität Heidelberg DE Germany (DE)

How to cite

APA:

Kuhns, S., Schmidt, K., Reymann, J., Gilbert, D., Neuner, A., Hub, B.,... Pereira, G. (2013). The microtubule affinity regulating kinase MARK4 promotes axoneme extension during early ciliogenesis. The Journal of Cell Biology, 200(4), 505-22. https://doi.org/10.1083/jcb.201206013

MLA:

Kuhns, S, et al. "The microtubule affinity regulating kinase MARK4 promotes axoneme extension during early ciliogenesis." The Journal of Cell Biology 200.4 (2013): 505-22.

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