Work

Rassf5 and Ndr kinases act in a novel pathway regulating neuronal polarity through Par3 phosphorylation

Year: 2014

Type: article

Abstract: The 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.

Source: Journal of Cell Science

DOI: 10.1242/jcs.146696

Authors: Rui Yang, Eryan Kong, Jing Jin, Alexander Hergovich, Andreas W. Püschel

Institutions: University of Münster, University College London

Language: English

Topic: Axon Guidance and Neuronal Signaling

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

Open Access status: green

Funder: Wellcome Trust

Award: Deciphering mammalian MST/hMOB1/NDR/LATS tumour suppressor networks.