The microtubule affinity regulating kinase MARK4 promotes axoneme extension during early ciliogenesis
| Autor: | Jürgen Reymann, Ursula Klingmüller, Birgit Hub, Michael Boutros, Stefanie Kuhns, Annett Neuner, Holger Erfle, Philipp Wiedemann, Kerstin Schmidt, Daniel Gilbert, Gislene Pereira, Hanswalter Zentgraf, Ricardo Carvalho |
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| Rok vydání: | 2013 |
| Předmět: |
Axoneme
Centriole Microtubule-associated protein Cell Cycle Proteins Protein Serine-Threonine Kinases Biology Models Biological Article Cell Line Mice Microtubule Ciliogenesis mental disorders Animals Humans Basal body Cilia Kinase activity Heat-Shock Proteins Research Articles Cilium Cell Biology Phosphoproteins Cell biology HEK293 Cells NIH 3T3 Cells RNA Interference Microtubule-Associated Proteins |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.201206013 |
| Popis: | A functional screen identified MARK4 as a positive regulator of axonemal extension and ciliogenesis via its interaction with the mother centriolar protein ODF2. 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. |
| Databáze: | OpenAIRE |
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