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RalA promotes a direct exocyst-Par6 interaction to regulate polarity in neuronal development

Research output: Contribution to journalArticle

Amlan Das, Sangeetha Gajendra, Katarzyna Falenta, Madeleine Oudin, Pascal Peschard, Shanshan Feng, Bin Wu, Christopher John Marshall, Patrick Doherty, Wei Guo, Giovanna Lalli

Original languageEnglish
Article numberN/A
Pages (from-to)686-699
Number of pages14
JournalJournal of Cell Science
Volume127
Issue number3
DOIs
Published1 Feb 2013

King's Authors

Abstract

Cell polarization is essential for neuronal development in both embryonic and postnatal brain. Here, using primary cultures, in vivo postnatal electroporation and conditional genetic ablation, we show that the Ras-like small GTPase RalA and its effector, the exocyst, regulate the morphology and polarized migration of neural progenitors derived from the subventricular zone, a major neurogenic niche in the postnatal brain. Active RalA promotes the direct binding between the exocyst subunit Exo84 and the PDZ domain of Par6 through a non-canonical PDZ-binding motif. Blocking the Exo84-Par6 interaction impairs polarization in postnatal neural progenitors and cultured embryonic neurons. Our results provide the first in vivo characterization of RalA function in the mammalian brain and highlight a novel molecular mechanism for cell polarization. Since the exocyst and the Par complex are conserved in many tissues, the functional significance of their interaction and its regulation by RalA are likely to be important in a wide range of polarization events.

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