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Mol Biol Cell ; 28(10): 1337-1346, 2017 May 15.
Article in English | MEDLINE | ID: mdl-28356421

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.


Subject(s)
Intracellular Signaling Peptides and Proteins/metabolism , Actins/metabolism , Animals , Cell Line , Cell Movement/physiology , Growth Cones/metabolism , Humans , Intracellular Signaling Peptides and Proteins/physiology , Mice , Molecular Chaperones/metabolism , Molecular Motor Proteins/metabolism , Myosin Heavy Chains/metabolism , Myosins/metabolism , Neurites/metabolism , Neurons/metabolism
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