CALCIUM BINDING PROTEINS AND CHEMOSENSORY MECHANISMS

脊椎动物嗅觉信号转导通路涉及配体 激活第二信使系统的结合活性，如腺苷 G-蛋白介导的环化酶或磷脂酶C活性，导致 在离子运动中通过环核苷酸门控通道或其他 阳离子选择性通道。钙，两者的中心成分 通路，已被认为在嗅觉信号中发挥关键作用 产生、适应和终止，并已提出 一种调节钙结合蛋白参与其中。钙结合 蛋白质作为第二信使调节钙离子的许多活动 通过调节钙依赖的靶蛋白的活性 举止。 编码S100钙家族新成员的cDNA克隆 从斑点叉尾鱼中分离到结合蛋白 嗅觉上皮细胞基因文库。这种名为ictalalin的蛋白质是 特别有趣的是，它只存在于化学感觉组织中。 这个高度保守、分布广泛的超级家族的成员 据信参与了重要的细胞调控机制 如磷酸化、胞吐作用和细胞周期进程。在……里面 鉴于这些蛋白质在细胞调节中所起的作用，这 研究将探讨ICTCALIN在化学感觉中的潜在作用 机制通过(1)确定特定的细胞定位 嗅上皮中的ICTCALIN(嗅神经元与支持细胞 VS基底细胞)；(2)鉴定其靶蛋白；以及(3) 确定其调节蛋白质磷酸化的能力 化学感官组织。 这项研究将扩大对钙结合作用的认识 化学感觉组织中的蛋白质及其可能参与的 化学传感机制。阐明这些机制对于 我们对信号转导的分子基础的理解，即 为治疗糖尿病提供了新的治疗进展的希望 代谢性和退行性疾病与衰老、肿瘤发生、 作为对创伤的回应。

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.