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

• Published in: Molecular biology of the cell 2017-05, Vol.28 (10), p.1337-1346
• Main Authors: Iizuka, Yoshie, Mooneyham, Ashley, Sieben, Andrew, Chen, Kevin, Maile, Makayla, Hellweg, Raffaele, Schütz, Florian, Teckle, Kebebush, Starr, Timothy, Thayanithy, Venugopal, Vogel, Rachel Isaksson, Lou, Emil, Lee, Michael K, Bazzaro, Martina
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.E16-06-0381

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.