UNC-45A is required for neurite extension via controlling NMII activation

Mol Biol Cell. 2017 May 15;28(10):1337-1346. doi: 10.1091/mbc.E16-06-0381. Epub 2017 Mar 29.

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.

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Line
  • Cell Movement / physiology
  • Growth Cones / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Intracellular Signaling Peptides and Proteins / physiology
  • Mice
  • Molecular Chaperones / metabolism
  • Molecular Motor Proteins / metabolism
  • Myosin Heavy Chains / metabolism
  • Myosins / metabolism
  • Neurites / metabolism
  • Neurons / metabolism

Substances

  • Actins
  • Intracellular Signaling Peptides and Proteins
  • MYH9 protein, human
  • Molecular Chaperones
  • Molecular Motor Proteins
  • UNC45A protein, human
  • Myosin Heavy Chains
  • Myosins