title: The cytoskeletal protein Ndel1 regulates dynamin 2 GTPase activity.
abstract: Cytoskeleton dynamics, membranes trafficking and positioning are essential for the proper functioning of any mammalian cell. The identification of the molecules and mechanisms that allow these cellular processes to interface is vital for understanding cell behaviors. Ndel1, the mammalian homolog of the Aspergillus nidulans NudE, organizes the cytoskeleton and regulates molecular motors, thereby impacting on the positioning of membranes. Hypothetically, Ndel1 can act in concert with enzymes controlling membrane trafficking (vesicle-mediated transport) per se, but this idea has never been investigated. We now report that a pool of Ndel1 associates directly with Dynamin 2 (Dyn2), a large cytosolic GTPase involved in the trafficking of the AMPA receptor subunit GluR1. In vitro, Ndel1 enhances Dyn2 GTPase activity in its unassembled and assembled forms, without promoting oligomerization of the enzyme. In cells, gain and loss of function of Ndel1 recapitulate the effects of overexpression of Dyn2 and Dyn2 dominant negative with reduced GTPase activity on the intracellular localization of GluR1, respectively, without affecting the stability of microtubules. Together, these results indicate that Ndel1 regulates Dyn2 GTPase activity and impacts GluR1-containing membranes distribution in a manner reminiscent of Dyn2.
authors.affiliation: Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Chansard
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Hong Chi
authors.initials: HC
authors.lastname: Tran
authors.forename: Gernot
authors.initials: G
authors.lastname: Neumayer
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Shim
authors.forename: Young-Un
authors.initials: YU
authors.lastname: Park
authors.forename: Camille
authors.initials: C
authors.lastname: Belzil
authors.forename: Hoa Thi
authors.initials: HT
authors.lastname: Le
authors.forename: Sang Ki
authors.initials: SK
authors.lastname: Park
authors.forename: Minh Dang
authors.initials: MD
authors.lastname: Nguyen
mesh_terms: D001692:Biological Transport; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D034285:Dynamin II / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D018091:Receptors, AMPA / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D034285:Dynamin II; D020558:GTP Phosphohydrolases; D018091:Receptors, AMPA; C421108:NDEL1 protein, human