Membrane contact site-dependent cholesterol transport regulates Na+/K+-ATPase polarization and spermiogenesis in Caenorhabditis elegans
Membrane contact site-dependent cholesterol transport regulates Na+/K+-ATPase polarization and spermiogenesis in Caenorhabditis elegans
复制标题
膜接触位点依赖性胆固醇转运调节秀丽隐杆线虫 Na /K -ATP 酶极化和精子发生
DOI：
10.1016/j.devcel.2021.05.002
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发表时间：
2021-06-07
影响因子：
11.8
通讯作者：
Miao, Long
中科院分区：
文献类型：
--
作者：
Wang, Qiushi;Cao, Zheng;Miao, Long
线虫精子发生是由圆形静止精子细胞分化为不对称爬行精子的过程。这种对称性破缺背后的分子机制仍然没有得到表征。在这项研究中，我们发现，精子特异性Na+/K+-ATP酶（NKA）是均匀分布在质膜（PM）的秀丽隐杆线虫精子细胞，但被移位，并随后进入内陷膜的精子细胞体在精子激活。NKA的极化依赖于胆固醇从PM通过膜接触位点（MCS）转运到膜细胞器（MO）。肌醇5-磷酸酶CIL-1和MO-定位的PI 4P磷酸酶SAC-1可以介导PI 4P代谢，以通过固醇/脂质转运蛋白驱动胆固醇通过MCS的反向转运。此外，NKA函数对于C是必需的。精子活力和繁殖成功率。我们的数据表明，MCSs介导的脂质动力学可能在细胞极性的建立中起着至关重要的作用。
Spermiogenesis in nematodes is a process whereby round and quiescent spermatids differentiate into asymmetric and crawling spermatozoa. The molecular mechanism underlying this symmetry breaking remains uncharacterized. In this study, we revealed that sperm-specific Na+/K+-ATPase (NKA) is evenly distributed on the plasma membrane (PM) of Caenorhabditis elegans spermatids but is translocated to and subsequently enters the invaginated membrane of the spermatozoa cell body during sperm activation. The polarization of NKA depends on the transport of cholesterol from the PM to membranous organelles (MOs) via membrane contact sites (MCSs). The inositol 5-phosphatase CIL-1 and the MO-localized PI4P phosphatase SAC-1 may mediate PI4P metabolism to drive cholesterol countertransport via sterol/lipid transport proteins through MCSs. Furthermore, the NKA function is required for C. elegans sperm motility and reproductive success. Our data imply that the lipid dynamics mediated by MCSs might play crucial roles in the establishment of cell polarity.