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

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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 microtu...

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Bibliographische Detailangaben
Hauptverfasser: Kuhns, Stefanie (VerfasserIn) , Reymann, Jürgen (VerfasserIn) , Neuner, Annett (VerfasserIn) , Erfle, Holger (VerfasserIn) , Boutros, Michael (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: February 11, 2013
In: The journal of cell biology
Year: 2013, Jahrgang: 200, Heft: 4, Pages: 505-522
ISSN:1540-8140
DOI:10.1083/jcb.201206013
Online-Zugang:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1083/jcb.201206013
Verlag, kostenfrei, Volltext: http://jcb.rupress.org/content/200/4/505
Volltext
Verfasserangaben:Stefanie Kuhns, Kerstin N. Schmidt, Jürgen Reymann, Daniel F. Gilbert, Annett Neuner, Birgit Hub, Ricardo Carvalho, Philipp Wiedemann, Hanswalter Zentgraf, Holger Erfle, Ursula Klingmüller, Michael Boutros, and Gislene Pereira
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 11.05.2017
Beschreibung:Online Resource
ISSN:1540-8140
DOI:10.1083/jcb.201206013

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