MYOSIN PHOSPHORYLATION IN THE NERVOUS SYSTEM

神经系统中的肌球蛋白磷酸化

• 批准号: 3476820
• 负责人: ARTHUR M EDELMAN
• 金额: $ 7.93万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1993-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3476820
• 关键词: calcium metabolism; calmodulin; central nervous system; cytoskeleton; laboratory rabbit; laboratory rat; myosins; nerve /myelin protein; neuroanatomy; phosphorylation; protein kinase

The identification of myosin and its discrete localization in neural tissues has stimulated research focused on a wide variety of possible functions for this protein including growth cone motility, exocytosis, dendritic shape changes and modulation of post- synaptic surface morphology. Neuronal myosin like other nonmuscle myosins may require phosphorylation of its light chain subunits in order to interact with actin and thus generate force. The initial phosphorylation event is therefore critically important in the regulation of the functions which myosin may subserve in neural tissue. We and others have identified several calcium- regulated protein kinases potentially capable of phosphorylating brain myosin, namely type II Ca2+, calmodulin-dependent kinase and myosin light chain kinase (MLCK). In order to explore this regulatory system we propose: 1) to detrmine the immunocytochemical localization of MLCK in the central nervous system, in cultured sympathetic neurons and in isolated brain subcellular fractions, 2) to study the sites and kinetics of the phosphorylation of brain myosin by brain MLCK and type II Ca2+, calmodulin-dependent kinase and 3) to study myosin phosphorylation and its cytoskeletal association in intact nerve endings as functions of depolarization and calcium influx. The results of this research will yield important information about a critical regulatory step in a number of fundamental functions of the neuronal cytoskeleton.

肌球蛋白及其在神经中的离散定位的识别 组织刺激了集中在各种各样的研究 该蛋白质的可能功能，包括生长锥运动， 胞吐作用，树突形状的变化和调节后的调节 突触表面形态。 神经元肌球蛋白像其他 非肌肉肌蛋白可能需要其轻链磷酸化 亚基为了与肌动蛋白相互作用并产生力。 因此，初始磷酸化事件至关重要 在调节肌球蛋白可能对的功能中 神经组织。我们和其他人已经确定了几个钙 - 调节的蛋白激酶可能能够磷酸化 脑肌球蛋白，即II型Ca2+，钙调蛋白依赖性激酶 和肌球蛋白轻链激酶（MLCK）。 为了探索这个 我们建议的监管系统：1） MLCK在中枢神经中的免疫细胞化学定位 系统，在培养的交感神经元和孤立的大脑中 亚细胞分数，2）研究的位点和动力学 脑MLCK和II型Ca2+对脑肌球蛋白的磷酸化， 钙调蛋白依赖性激酶和3）研究肌球蛋白 完整神经中的磷酸化及其细胞骨架关联 结尾是去极化和钙涌入的功能。 这 这项研究的结果将产生有关 许多基本功能的关键调节步骤 神经元细胞骨架。