학술논문

Regulation of axon growth by myosin II-dependent mechanocatalysis of cofilin activity.
Document Type
Article
Source
Journal of Cell Biology. Jul2019, Vol. 218 Issue 7, p2329-2349. 21p.
Subject
*AXONS
*GROWTH rate
*CONES
*THERAPEUTICS
Language
ISSN
0021-9525
Abstract
Serotonin (5-HT) is known to increase the rate of growth cone advance via cofilin-dependent increases in retrograde actin network flow and nonmuscle myosin II activity. We report that myosin II activity is regulated by PKC during 5-HT responses and that PKC activity is necessary for increases in traction force normally associated with these growth responses. 5-HT simultaneously induces cofilin-dependent decreases in actin network density and PKC-dependent increases in point contact density. These reciprocal effects facilitate increases in traction force production in domains exhibiting decreased actin network density. Interestingly, when PKC activity was up-regulated, 5-HT treatments resulted in myosin II hyperactivation accompanied by catastrophic cofilin-dependent decreases in actin filament density, sudden decreases in traction force, and neurite retraction. These results reveal a synergistic relationship between cofilin and myosin II that is spatiotemporally regulated in the growth cone via mechanocatalytic effects to modulate neurite growth. [ABSTRACT FROM AUTHOR]