Rassf5 and Ndr kinases regulate neuronal polarity through Par3 phosphorylation in a novel pathway.
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2014 Aug 15;127(Pt 16):3463-76. doi: 10.1242/jcs.146696. Epub
2014 Jun 13.Rassf5 and Ndr kinases regulate neuronal polarity through Par3 phosphorylation in a novel pathway.1, 1, 1, 2, 3.1Institut für Molekulare Zellbiologie, Westf?lische Wilhelms-Universit?t Münster, Schlossplatz 5, D-48149 Münster, Germany.2UCL Cancer Institute, University College London, London WC1E 6BT, UK.3Institut für Molekulare Zellbiologie, Westf?lische Wilhelms-Universit?t Münster, Schlossplatz 5, D-48149 Münster, Germany Cells-in-Motion Cluster of Excellence, University of Münster, D-48149 Münster, Germany apuschel@uni-muenster.de.AbstractThe morphology and polarized growth of cells depend on pathways that control the asymmetric distribution of regulatory factors. The evolutionarily conserved Ndr kinases play important roles in cell polarity and morphogenesis in yeast and invertebrates but it is unclear whether they perform a similar function in mammalian cells. Here, we analyze the function of mammalian Ndr1 and Ndr2 (also known as STK38 or STK38L, respectively) in the establishment of polarity in neurons. We show that they act downstream of the tumor suppressor Rassf5 and upstream of the polarity protein Par3 (also known as PARD3). Rassf5 and Ndr1 or Ndr2 are required during the polarization of hippocampal neurons to prevent the formation of supernumerary axons. Mechanistically, the Ndr kinases act by phosphorylating Par3 at Ser383 to inhibit its interaction with dynein, thereby polarizing the distribution of Par3 and reinforcing axon specification. Our results identify a novel Rassf5-Ndr-Par3 signaling cascade that regulates the transport of Par3 during the establishment of neuronal polarity. Their role in neuronal polarity suggests that Ndr kinases perform a conserved function as regulators of cell polarity. (C) 2014. Published by The Company of Biologists Ltd.KEYWORDS: A C N ParPMID:
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