The function of cAMP and Ca2+ in motility of human sperm

cAMP 和 Ca2 在人类精子运动中的作用

• 批准号: 41161011
• 负责人: Professor Dr. Ulrich Benjamin Kaupp
• 金额: --
• 依托单位: Abteilung für Chemische Biologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 无数据
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/41161011?language=en
• 关键词: function; cAMP; Ca2+; motility; human

Cyclic nucleotides and Ca2+ play key roles in chemotactic signaling of sperm from marine invertebrates. While these messenger molecules have also been invoked in chemotaxis of mammalian sperm, our knowledge is either fragmentary or controversial. We propose here to study the function of cAMP and Ca2+ in motility and chemotaxis of human sperm. Using kinetic techniques and caged compounds, we will examine the motor response evoked by a rapid step increase of either cAMP or Ca2+ in the sperm flagellum. We will study the cAMP response of sperm stimulated with putative chemoattractants and activators of adenylyl cyclases. Furthermore, we will examine the mechanisms by which either putative chemoattractants or cAMP elevate intracellular Ca2+ concentration using fluorescent potentiometric probes and Ca2+ dyes.Our earlier studies demonstrated that mammalian spermatozoa are capable of being guided to the oocyte at the fertilization site by two active processes; chemotaxis and thermotaxis. The molecular mechanisms underlying these processes are obscure. Our aim is to reveal molecular steps in these mechanisms and to determine their sequence. To this end we will apply rapid-mixing techniques to look for changes in the levels of potential second messengers, which occur within the time scale of the swimming response of human spermatozoa to a change in chemoattractant concentration (for chemotaxis) or to a temperature shift (for thermotaxis). We will also try to identify the sperm thermosensors used by the cell for thermotaxis. The information gained is expected to contribute new perspectives to our understanding of mammalian reproduction and to have potential future implications to diagnosing and treating human fertility.

环核苷酸和Ca ~（2+）在海洋无脊椎动物精子趋化信号中起关键作用。虽然这些信使分子也被调用在哺乳动物精子的趋化性，我们的知识是零碎的或有争议的。本文拟研究cAMP和Ca ~（2+）在人精子运动和趋化中的作用。使用动力学技术和笼化合物，我们将检查运动反应引起的快速步骤增加的cAMP或Ca 2+在精子鞭毛。我们将研究cAMP反应的精子刺激与假定的化学引诱剂和激活剂的腺苷酸环化酶。此外，我们将研究的机制，无论是假定的化学引诱剂或cAMP升高细胞内Ca 2+浓度使用荧光电位探针和Ca 2 + dyeers.Our早期的研究表明，哺乳动物精子能够被引导到卵母细胞的受精位点通过两个活跃的过程：趋化性和趋热性。这些过程背后的分子机制是模糊的。我们的目标是揭示这些机制中的分子步骤，并确定它们的序列。为此，我们将应用快速混合技术来寻找潜在的第二信使的水平的变化，这发生在人类精子的游泳反应的时间尺度内，以改变趋化剂浓度（趋化性）或温度变化（趋热性）。我们还将尝试识别细胞用于趋热性的精子温度传感器。所获得的信息有望为我们理解哺乳动物生殖提供新的视角，并对诊断和治疗人类生育能力具有潜在的未来影响。