Crosstalk of Calcium and other pathways in capacitation

钙和其他获能途径的串扰

• 批准号: 8697214
• 负责人: Pablo E. Visconti
• 金额: $ 31.28万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8697214
• 关键词: Acrosome; Acrosome Reaction; Adenylate Cyclase; Affect; Agonist; Antibiotic A23187; Assisted Reproductive Technology; Biochemical; Biological Assay; Bypass; Ca(2+)-Transporting ATPase; Calcium; CatSper; Cell membrane; Characteristics; Complex; Comprehension; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Egtazic Acid; Ejaculation; Event; Extracellular Space; Female; Fertilization; Fertilization in Vitro; Flagella; Flow Cytometry; Generations; Goals; Homeostasis; In Vitro; Infertility; Investigation; Ionophores; Ions; Knock-out; Knockout Mice; Knowledge; Life; Mediating; Membrane Potentials; Methodology; Methods; Molecular; Movement; Mus; Pathway interactions; Pattern; Phosphorylation; Physiologic pulse; Physiology; Play; Population; Preparation; Process; Protein Family; Protocols documentation; Reagent; Regulation; Research; Role; Signal Pathway; Sperm Capacitation; Sterility; System; Therapeutic; Time; Tyrosine Phosphorylation; Up-Regulation; Work; base; cell motility; contraceptive target; design; driving force; egg; extracellular; improved; male; mouse model; novel; optical traps; patch clamp; public health relevance; single cell analysis; sperm cell; tool; zygote

DESCRIPTION (provided by applicant): Mammalian sperm are not able to fertilize eggs immediately after ejaculation. They acquire fertilization capacity in the female tract in a process known as capacitation. Initially, capacitation was defined using fertilization as an end-point. However, a variety of evidence suggests that the functional changes occurring in the sperm during capacitation are not one event, but a combination of sequential and concomitant processes. These processes are associated with changes in the motility pattern (e.g. hyperactivation) and with preparation of sperm to undergo an agonist-stimulated acrosome reaction. At the molecular level, capacitation is associated with the activation of a cAMP signaling pathway, increase in intracellular pH, changes in the sperm plasma membrane potential, increase in tyrosine phosphorylation and with up-regulation of intracellular Ca2+ concentration ([Ca2+]i). In particular Ca2+ plays central roles in the regulation of both hyperactivation and the AR. However, the molecular mechanisms that control [Ca2+]i in sperm are not well established. The central hypothesis underlying this proposal posits that hyperactivation is the consequence of crosstalk between cAMP and Ca2+-depending signaling pathways. The objective of this proposal is to understand how Ca2+ and other signaling pathways (e.g. increase in pHi, cAMP and changes in Em) integrate during capacitation.

描述（由申请人提供）：哺乳动物精子在射精后不能立即使卵子受精。它们在雌性生殖道中获得受精能力 称为获能。最初，获能被定义为使用受精作为终点。然而，各种证据表明，在获能过程中精子发生的功能变化不是一个事件，而是一个顺序和伴随过程的组合。这些过程与运动模式的变化（例如超活化）和精子准备进行激动剂刺激的顶体反应有关。在分子水平上，获能与cAMP信号通路的激活、细胞内pH的增加、精子质膜电位的变化、酪氨酸磷酸化的增加以及细胞内Ca 2+浓度（[Ca 2 +]i）的上调相关。特别是Ca2+在超活化和AR的调节中起核心作用。然而，控制精子中[Ca2+]i的分子机制还没有很好地建立。该提议的核心假设假定，超活化是cAMP和Ca2+依赖性信号通路之间串扰的结果。本提案的目的是了解在获能过程中Ca2+和其他信号通路（例如pHi，cAMP的增加和Em的变化）如何整合。