Loss of annexin A7 leads to alterations in frequency-induced shortening of isolated murine cardiomyocytes
Loss of annexin A7 leads to alterations in frequency-induced shortening of isolated murine cardiomyocytes
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DOI：
10.1128/mcb.21.13.4119-4128.2001
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发表时间：
2001-07-01
影响因子：
5.3
通讯作者：
Noegel, AA
中科院分区：
文献类型：
--
作者：
Herr, C;Smyth, N;Noegel, AA
已经提出膜联蛋白A7在囊泡的融合中起作用，作为Ca 2+通道和Ca 2+激活的GTP酶，从而诱导Ca 2 +/GTP依赖性分泌事件。为了了解膜联蛋白A7的功能，我们在小鼠中对Anxa 7基因进行了靶向破坏。杂合子小鼠之间的交配产生的后代表现出正常的孟德尔遗传模式，表明膜联蛋白A7的丢失不会干扰子宫内的生存能力。缺乏膜联蛋白A7的小鼠没有表现出明显的表型，并且具有生育能力。为了测定胞吐作用，检查了来自分离的胰岛的胰岛素分泌。钙离子诱导和环AMP介导的胰岛素分泌的增强在膜联蛋白A7的情况下是不变的，这表明它不直接参与囊泡融合。在分离的心肌细胞中研究的Ca 2+调节表明，虽然来自早期胚胎的细胞显示出完整的Ca 2+稳态，并表达兴奋-收缩偶联所需的所有成分，但来自成年Anra 7（-/-）小鼠的心肌细胞在高频刺激时表现出改变的细胞缩短-频率关系。这表明膜联蛋白A7在机电耦合中的功能，可能是通过Ca 2+稳态。
Annexin A7 has been proposed to function in the fusion of vesicles, acting as a Ca2+ channel and as Ca2+-activated GTPase, thus inducing Ca2+/GTP-dependent secretory events. To understand the function of annexin A7, we have performed targeted disruption of the Anxa7 gene in mice. Matings between heterozygous mice produced offspring showing a normal Mendelian pattern of inheritance, indicating that the loss of annexin A7 did not interfere with viability in utero. Mice lacking annexin A7 showed no obvious phenotype and were fertile. To assay for exocytosis, insulin secretion from isolated islets of Langerhans was examined. Ca2+-induced and cyclic AMP-mediated potentiation of insulin secretion was unchanged in the absence of annexin A7, suggesting that it is not directly implicated in vesicle fusion. Ca2+ regulation studied in isolated cardiomyocytes, showed that while cells from early embryos displayed intact Ca2+ homeostasis and expressed all of the components required for excitation-contraction coupling, cardiomyocytes from adult Anra7(-/-) mice exhibited an altered cell shortening-frequency relationship when stimulated with high frequencies. This suggests a function for annexin A7 in electromechanical coupling, probably through Ca2+ homoeostasis.