MECHANISMS OF ADAPTATION AND EXCITATION

描述(改编自申请人的摘要)：这项提案将 继续对光传导机制的长期研究 光感受器。CaM-Kinase被认为参与了 Arrestin的磷酸化依赖于光，但其功能尚不清楚。 CaM-K在调节等效光和其他信号转导中的可能作用 信号转导过程将通过细胞内注射活性物质进行测试 激活剂或激活剂。第二组实验将试图 阐明仍不清楚的转导的后期阶段。这些 实验是基于这样一个假设，即钙离子升高 由磷脂酶C(PLC)-IP3途径产生的产物触发了一个循环酶； 由此产生的环核苷酸的升高可以激活环 在早期实验中观察到的核苷酸门控通道 帕奇斯。如果得到证实，这一假设将提供一条完整的途径 从视紫红质到经络和理解变性的框架 无脊椎动物的由光产生的。最后一组实验建立在 早些时候的观察表明，Cam也可能参与了 转导。建议进行生理生化实验，以 本地化此步骤。初步证据表明，可能是在PLC。 如果这些结果得到证实，可能会揭示出全新的监管机制 对于磷脂酶和钙离子，洞察力可能对理解 这种酶在脊椎动物锥体中的作用，在那里它的作用仍然存在 完全不清楚。

DESCRIPTION (Adapted from applicant's abstract): This proposal would continue a long-term investigation of phototransduction mechanisms in Limulus photoreceptors. CaM-kinase has been implicated in the light-dependent phosphorylation of arrestin, but its function is unknown. The possible role of CaM-kinase in regulating equivalent light and other transduction processes will be tested by intracellular injection of active kinase or kinase inhibitors. A second set of experiments will attempt to elucidate the late stages of transduction which remain unknown. These experiments are predicated on the hypothesis that the Ca2+ elevation produced by the phospholipase C (PLC)-IP3 pathway triggers a cyclase; the resulting elevation of cyclic nucleotide could activate the cyclic nucleotide-gated channels observed in earlier experiments on excised patches. If confirmed, this hypothesis would provide a complete pathway from rhodopsin to channel and a framework for understanding the degeneration produced by light in invertebrates. A final set of experiments builds upon the earlier observation that CaM may also be involved in an early step of transduction. Physiological and biochemical experiments are proposed to localize this step. Preliminary evidence suggests that it may be at PLC. These results, if confirmed, may reveal altogether new regulatory mechanisms for phospholipase and Ca2+, insight that may be important in understanding the role of this enzyme in vertebrate cones, where its role remains completely unclear.