Modulation of actomyosin contractility by myosin light chain phosphorylation/dephosphorylation through Rho GTPases signaling specifies axon formation in neurons.
Actin depolymerization through Rho GTPases or exogenous mechanical tension has been suggested as a key determinant for the first step of neuronal polarization, the axonogenesis, in which one of the neurites starts to grow becoming the axon. The underlying mechanism and the relationship between two forces in the cells, however, are mostly unknown. Here, we report that the myosin-dependent contractility is a common effector between two forces and a critical determinant in axonogenesis and neuronal polarization. We have found that inhibition of myosin ATPase activity and modulation of myosin light chain phosphorylation/dephosphorylation through Rho GTPases signaling induced multiple axons. Moreover, overexpression of wild-type myosin light chain kinase dramatically increased filopodial structures and produced multi-axonal structures. Our results suggest that MLC phosphorylation/dephosphorylation through Rho GTPases signaling modulates the actomyosin contractility, and then in turn provides a physiological tension in neurons to induce axon.
Kim
Yujin
Y
Department of Life Science, Gwangju Institute of Science and Technology, 1 Oryong-dong Buk-gu, Gwangju 500-712, Republic of Korea.
Chang
Sunghoe
S
D000205:Actomyosin / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005333:Fetus / Q000166:cytology; D006624:Hippocampus / Q000166:cytology; D018994:Myosin Light Chains / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000235:genetics / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009218:Myosins / Q000037:antagonists & inhibitors / Q000378:metabolism; D016501:Neurites / Q000502:physiology / Q000648:ultrastructure; D009474:Neurons / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D010766:Phosphorylation; D011714:Pyrans / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction; D013141:Spiro Compounds / Q000494:pharmacology; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D004791:Enzyme Inhibitors; D018994:Myosin Light Chains; D011714:Pyrans; D013141:Spiro Compounds; C053079:tautomycin; C004717:diacetylmonoxime; D000205:Actomyosin; D009219:Myosin-Light-Chain Kinase; D043263:Myosin-Light-Chain Phosphatase; D009218:Myosins; D020741:rho GTP-Binding Proteins; D003931:Diacetyl