Carvacho Ingrid, Lee Hoi Chang, Fissore Rafael A, Clapham David E
Howard Hughes Medical Institute, Department of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
Cell Rep. 2013 Dec 12;5(5):1375-86. doi: 10.1016/j.celrep.2013.11.007. Epub 2013 Dec 5.
In mammals, calcium influx is required for oocyte maturation and egg activation. The molecular identities of the calcium-permeant channels that underlie the initiation of embryonic development are not established. Here, we describe a transient receptor potential (TRP) ion channel current activated by TRP agonists that is absent in TrpV3(-/-) eggs. TRPV3 current is differentially expressed during oocyte maturation, reaching a peak of maximum density and activity at metaphase of meiosis II (MII), the stage of fertilization. Selective activation of TRPV3 channels provokes egg activation by mediating massive calcium entry. Widely used to activate eggs, strontium application is known to yield normal offspring in combination with somatic cell nuclear transfer. We show that TRPV3 is required for strontium influx, because TrpV3(-/-) eggs failed to conduct Sr(2+) or undergo strontium-induced activation. We propose that TRPV3 is a major mediator of calcium influx in mouse eggs and is a putative target for artificial egg activation.
在哺乳动物中,卵母细胞成熟和卵子激活需要钙内流。启动胚胎发育的钙通透通道的分子特性尚未明确。在此,我们描述了一种由TRP激动剂激活的瞬时受体电位(TRP)离子通道电流,该电流在TrpV3基因敲除(-/-)的卵子中不存在。TRPV3电流在卵母细胞成熟过程中差异表达,在减数分裂II中期(MII)即受精阶段达到最大密度和活性的峰值。TRPV3通道的选择性激活通过介导大量钙内流引发卵子激活。锶广泛用于激活卵子,已知其与体细胞核移植结合可产生正常后代。我们发现TRPV3是锶内流所必需的,因为TrpV3基因敲除(-/-)的卵子无法传导Sr(2+)或经历锶诱导的激活。我们提出TRPV3是小鼠卵子中钙内流的主要介质,并且是人工卵子激活的一个假定靶点。