Regulation of axon growth by myosin II–dependent mechanocatalysis of cofilin activity
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 23, 2019
- Source ID
- 10.1083/jcb.201810054
Entities
People
- Arash Fereydooni
- Enrique M. De La Cruz
- Michael Murrell
- Nicole Tsai
- Paul Forscher
- Visar Ajeti
- William Burns
- Xiao-feng Zhang
Organizations
- Army Research Office
- National Institutes of Health
- United States Department of Defense
- University of California, San Francisco
- University of Connecticut
- Yale University