• Ketakee Ghate, Sampada P Mutalik, SthanamLakshmi KavithaLKDepartment of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Bombay, Mumbai 400076, India., Shamik Sen, and Aurnab Ghose.
• Indian Institute of Science Education and Research (IISER) Pune, Dr. Homi Bhabha Road, Pune 411008, India.
• Neuroscience. 2020 Nov 10; 448: 160-171.

AbstractGrowth cone-mediated axonal outgrowth and accurate synaptic targeting are central to brain morphogenesis. Translocation of the growth cone necessitates mechanochemical regulation of cell-extracellular matrix interactions and the generation of propulsive traction forces onto the growth environment. However, the molecular mechanisms subserving force generation by growth cones remain poorly characterized. The formin family member, Fmn2, has been identified earlier as a regulator of growth cone motility. Here, we explore the mechanisms underlying Fmn2 function in the growth cone. Evaluation of multiple components of the adhesion complexes suggests that Fmn2 regulates point contact stability. Analysis of F-actin retrograde flow reveals that Fmn2 functions as a clutch molecule and mediates the coupling of the actin cytoskeleton to the growth substrate, via point contact adhesion complexes. Using traction force microscopy, we show that the Fmn2-mediated clutch function is necessary for the generation of traction stresses by neurons. Our findings suggest that Fmn2, a protein associated with neurodevelopmental and neurodegenerative disorders, is a key regulator of a molecular clutch activity and consequently motility of neuronal growth cones.Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.

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