Sperm-activating peptides in the regulation of ion fluxes, signal transduction and motility
Sperm-activating peptides in the regulation of ion fluxes, signal transduction and motility
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DOI：
10.1387/ijdb.072550ad
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发表时间：
2008-01-01
影响因子：
0.7
通讯作者：
Wood, Christopher D.
中科院分区：
文献类型：
--
作者：
Darszon, Alberto;Guerrero, Adan;Wood, Christopher D.
棘皮动物的精子使用环核苷酸（CNs）作为重要的第二信使来定位和游向卵子。海胆精子中含有丰富的膜结合胍基环化酶（mGC），这种酶是由David Garbers小组首次从海胆睾丸中克隆出来的。他的研究小组还发现了精子，这是第一个从卵子投资（或蛋胶）中分离出来的精子激活肽（SAP）。这种十肽刺激精子mGC，引起cGMP的快速瞬时增加，触发一系列精心安排的生理反应，包括膜电位、细胞内pH （pHi）、细胞内Ca2+浓度（[Ca2+]i）和cAMP水平的变化。多个小组的证据表明，cGMP激活K+选择通道是SAPs诱导的信号级联中第一个离子通透性变化，最近候选基因终于被确定。该通道的4个重复的6个跨膜片段中的每一个都包含一个环核苷酸结合域。它们一起构成了一个单一的多肽链，就像电压门控的Na+或Ca2+通道一样。这种名为tetraKCNG的新型通道似乎属于仅在精子及其祖细胞中表达的新型蛋白质家族的专属俱乐部。sap还诱导鞭毛[Ca2+]i的波动，这与鞭毛形态的变化有关，并调节精子轨迹。运动的变化取决于[Ca2+]i通过特定的Ca2+通道流入，而不是精子鞭毛的整体[Ca2+]i。所有纤毛和鞭毛都有一个保守的轴突结构，因此了解Ca2+如何调节纤毛和鞭毛的跳动是一个基本问题。
Echinoderm sperm use cyclic nucleotides (CNs) as essential second messengers to locate and swim towards the egg. Sea urchin sperm constitute a rich source of membrane-bound guanylyl cyclase (mGC), which was first cloned from sea urchin testis by the group of David Garbers. His group also identified speract, the first sperm-activating peptide (SAP) to be isolated from the egg investment (or egg jelly). This decapeptide stimulates sperm mGC causing a fast transient increase in cGMP that triggers an orchestrated set of physiological responses including: changes in: membrane potential, intracellular pH (pHi), intracellular Ca2+ concentration ([Ca2+]i) and cAMP levels. Evidence from several groups indicated that cGMP activation of a K+ selective channel was the first ion permeability change in the signaling cascade induced by SAPs, and recently the candidate gene was finally identified. Each of the 4 repeated, 6 trans-membrane segments of this channel contains a cyclic nucleotide binding domain. Together they comprise a single polypeptide chain like voltage-gated Na+ or Ca2+ channels. This new type of channel, named tetraKCNG, appears to belong to the exclusive club of novel protein families expressed only in sperm and its progenitors. SAPs also induce fluctuations in flagellar [Ca2+]i that correlate with changes in flagellar form and regulate sperm trajectory. The motility changes depend on [Ca2+]i influx through specific Ca2+ channels and not on the overall [Ca2+]i in the sperm flagellum. All cilia and flagella have a conserved axonemal structure and thus understanding how Ca2+ regulates cilia and flagella beating is a fundamental question.