부산대학교 도서관

Chondroitin sulfate proteoglycans (CSPGs) are major components of the extracellular matrix in the CNS that inhibit axonal regeneration after CNS injury. Signaling pathways in neurons triggered by CSPGs are still largely unknown. In this study, using well-characterized in vitro assays for neurite outgrowth and neurite guidance, we demonstrate a major role for myosin II in the response of neurons to CSPGs. We found that the phosphorylation of myosin II regulatory light chains is increased by CSPGs. Specific inhibition of myosin II activity with blebbistatin allows growing neurites to cross onto CSPG-rich areas and increases the length of neurites of neurons growing on CSPGs. Using specific gene knockdown, we demonstrate selective roles for myosin IIA and IIB in these processes. Time lapse microscopy and immunocytochemistry demonstrated that CSPGs also inhibit cell adhesion and cell spreading. Inhibition of myosin II selectively accelerated neurite initiation without altering cell adhesion and spreading on CSPGs. : Chondroitin sulfate proteoglycans (CSPGs) play a negative role in axon guidance and regeneration. We demonstrate that these actions of CSPGs are dependent upon myosin II activity as CSPGs increase the phosphorylation of myosin light chains and inhibition of myosin II activity promotes growth on CSPGs. These results extend our knowledge of the role of cytoskeletal motor proteins in response to inhibitory axon guidance molecules.(Figure is included in full-text article.)