title: RalA promotes a direct exocyst-Par6 interaction to regulate polarity in neuronal development.
abstract: Cell polarization is essential for neuronal development in both the 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. Given that 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.
authors.affiliation: University of Pennsylvania Department of Biology, Philadelphia, PA 19104, USA.
authors.forename: Amlan
authors.initials: A
authors.lastname: Das
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Gajendra
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Falenta
authors.forename: Madeleine J
authors.initials: MJ
authors.lastname: Oudin
authors.forename: Pascal
authors.initials: P
authors.lastname: Peschard
authors.forename: Shanshan
authors.initials: S
authors.lastname: Feng
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Marshall
authors.forename: Patrick
authors.initials: P
authors.lastname: Doherty
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lalli
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D016764:Cell Polarity / Q000235:genetics; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism*; D054731:PDZ Domains / Q000235:genetics; D061251:Primary Cell Culture; D011485:Protein Binding; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000378:metabolism; D020725:ral GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C518597:Par6 protein, mouse; D033921:Vesicular Transport Proteins; C118120:Rala protein, mouse; D020725:ral GTP-Binding Proteins
keywords: Exocyst; Neuroblast migration; Neuronal polarity; Par6; Ral