title: UNC-45A is required for neurite extension via controlling NMII activation.
abstract: UNC-45A is a highly conserved member of the UNC-45/CRO1/She4p family of proteins, which act as chaperones for conventional and nonconventional myosins. NMII mediates contractility and actin-based motility, which are fundamental for proper growth cone motility and neurite extension. The presence and role of UNC-45A in neuronal differentiation have been largely unknown. Here we demonstrate that UNC-45A is a novel growth cone--localized, NMII-associated component of the multiprotein complex regulating growth cone dynamics. We show that UNC-45A is dispensable for neuron survival but required for neurite elongation. Mechanistically, loss of UNC-45A results in increased levels of NMII activation. Collectively our results provide novel insights into the molecular mechanisms of neurite growth and define UNC-45A as a novel and master regulator of NMII-mediated cellular processes in neurons.
authors.affiliation: Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Heath, University of Minnesota Twin Cities, Minneapolis, MN 55455.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Iizuka
authors.affiliation: Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Heath, University of Minnesota Twin Cities, Minneapolis, MN 55455.
authors.forename: Ashley
authors.initials: A
authors.lastname: Mooneyham
authors.affiliation: Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Heath, University of Minnesota Twin Cities, Minneapolis, MN 55455.
authors.forename: Andrew
authors.initials: A
authors.lastname: Sieben
authors.affiliation: Department of Biology, University of Maryland, Baltimore, MD 21250.
authors.forename: Kevin
authors.initials: K
authors.lastname: Chen
authors.affiliation: Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Heath, University of Minnesota Twin Cities, Minneapolis, MN 55455.
authors.forename: Makayla
authors.initials: M
authors.lastname: Maile
authors.affiliation: Breast Unit, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Hellweg
authors.affiliation: Breast Unit, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schütz
authors.affiliation: Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Heath, University of Minnesota Twin Cities, Minneapolis, MN 55455.
authors.forename: Kebebush
authors.initials: K
authors.lastname: Teckle
authors.affiliation: Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Heath, University of Minnesota Twin Cities, Minneapolis, MN 55455.
authors.forename: Timothy
authors.initials: T
authors.lastname: Starr
authors.affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota Twin Cities, Minneapolis, MN 55455.
authors.forename: Venugopal
authors.initials: V
authors.lastname: Thayanithy
authors.affiliation: Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Heath, University of Minnesota Twin Cities, Minneapolis, MN 55455.
authors.forename: Rachel Isaksson
authors.initials: RI
authors.lastname: Vogel
authors.affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota Twin Cities, Minneapolis, MN 55455.
authors.forename: Emil
authors.initials: E
authors.lastname: Lou
authors.affiliation: Department of Neuroscience, University of Minnesota Twin Cities, Minneapolis, MN 55455.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Lee
authors.affiliation: Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Heath, University of Minnesota Twin Cities, Minneapolis, MN 55455 mbazzaro@umn.edu.
authors.forename: Martina
authors.initials: M
authors.lastname: Bazzaro
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D020439:Growth Cones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism; D020409:Molecular Motor Proteins / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000378:metabolism
chemical_list: D000199:Actins; D047908:Intracellular Signaling Peptides and Proteins; C103814:MYH9 protein, human; D018832:Molecular Chaperones; D020409:Molecular Motor Proteins; C509158:UNC45A protein, human; D018995:Myosin Heavy Chains; D009218:Myosins