MLCK/MLCP regulates mammalian axon regeneration via the redistribution of the growth cone F-actin

Abstract

Axon regrowth is a key determinant of the restoration of the biological function of the nervous system after trauma. However, mature mammalian neurons have limited capacity for axon regeneration. We have previously demonstrated that neuronal axon growth both in the central and the peripheral nervous systems is markedly enhanced when non-muscle myosin II (NMII) is inhibited with blebbistatin. The activity of NMII is primarily regulated by MLCK and MLCP via the phosphorylation and dephosphorylation of its light chain, respectively; however, the functional roles of MLCK and MLCP in mammalian axonal regeneration remain unknown. In the present study, we provide strong evidence that the inhibition of MLCK activity significantly blocks axon regeneration in the mouse. Conversely, inhibition of MLCP promotes axon regrowth of both peripheral and central nervous system. Our findings further indicate that the MLCK/MLCP regulates axon regeneration via the reorganization of F-actin distribution in the growth cone, and this result suggests that direct regulation of the growth cone machinery is a potential strategy to promote axon regeneration.