CALCIUM BINDING PROTEINS AND CHEMOSENSORY MECHANISMS

钙结合蛋白和化学感应机制

• 批准号: 2014816
• 负责人: ANGELA R PORTA
• 金额: $ 3.68万
• 依托单位: KEAN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-01 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2014816
• 关键词: calcium binding protein; catfish; complementary DNA; epithelium; gene expression; genetic library; gills; immunocytochemistry; in situ hybridization; olfactions; olfactory stimulus; phosphorylation; skin

Vertebrate olfactory signal transduction pathways involve ligand binding activity that activates second messenger systems such adenylate cyclase or phospholipase C activity mediated by G-proteins, resulting in ion movements through cyclic nucleotide gated channels or other cation-selective channels. Calcium, a central component to both pathways, has been implicated to play a key role in olfactory signal generation, adaptation and termination and it has been proposed that a regulatory calcium binding protein is involved. Calcium binding proteins mediate many of the actions of calcium as a second messenger by modulating the activity of target proteins in a calcium dependent manner. A cDNA clone encoding a novel member of the S100 family of calcium binding proteins has been isolated from a catfish (Ictalurus punctatus) olfactory epithelium cDNA library. This protein, named ictacalcin, is particularly interesting as it is present only in chemosensory tissue. Members of this highly conserved, widely distributed superfamily are believed to participate in important cellular regulatory mechanisms such as phosphorylation, exocytosis and cell cycle progression. In light of the role that these proteins play in cell regulation , this study will investigate the potential role of ictacalcin in chemosensory mechanisms by (1) determining the specific cellular localization of ictacalcin in olfactory epithelium (olfactory neurons vs. support cells vs basal cells); (2) identifying its target proteins; and (3) determining its ability to modulate the phosphorylation of proteins in chemosensory tissue. This study will expand knowledge of the role of calcium binding proteins in chemosensory tissue and their possible involvement in chemosensory mechanisms. Elucidating these mechanisms is critical to our understanding of the molecular basis of signal transduction, which offers the promise for novel therapeutic advances in the treatment of metabolic and degenerative diseases associated with aging, oncogenesis, and in response to trauma.

脊椎动物嗅觉信号传导途径涉及配体 激活第二信使系统如腺苷酸的结合活性 由G蛋白介导的环化酶或磷脂酶C活性， 在通过环核苷酸门控通道或其它通道的离子运动中， 阳离子选择性通道钙，一个核心组成部分， 在嗅觉信号传导中起着关键作用 产生、适应和终止，并且已经提出， 涉及调节性钙结合蛋白。钙结合 蛋白质作为第二信使介导钙的许多作用 通过调节靶蛋白的活性， 方式 一个编码钙离子S100家族新成员的cDNA克隆 结合蛋白已经从鲶鱼（Ictalurus punctatus）中分离出来， 嗅上皮cDNA文库这种蛋白质被命名为ictacalcin， 特别令人感兴趣的是，因为它仅存在于化学感受组织中。 这个高度保守、广泛分布的超家族的成员是 据信参与重要的细胞调节机制 如磷酸化、胞吐作用和细胞周期进程。在 鉴于这些蛋白质在细胞调节中的作用， 这项研究将调查ictacalcin在化学感受中的潜在作用。 （1）确定特定的细胞定位， 嗅上皮细胞中的伊卡钙蛋白（嗅神经元与支持细胞 vs基底细胞）;（2）鉴定其靶蛋白;和（3） 确定其调节蛋白质磷酸化的能力， 化学感受组织 这项研究将扩大知识的作用，钙结合 化学感受组织中的蛋白质及其可能参与 化学感受机制阐明这些机制对于 我们对信号转导的分子基础的理解， 提供了新的治疗进展的希望，在治疗 与衰老，肿瘤发生， and in response响应to trauma创伤.