Shum Winnie W C, Da Silva Nicolas, Brown Dennis, Breton Sylvie
Center for Systems Biology, Program in Membrane Biology, Nephrology Division, Massachusetts General Hospital, Boston, MA 02114, USA.
J Exp Biol. 2009 Jun;212(Pt 11):1753-61. doi: 10.1242/jeb.027284.
In the epididymis, spermatozoa acquire their ability to become motile and to fertilize an egg. A luminal acidic pH and a low bicarbonate concentration help keep spermatozoa in a quiescent state during their maturation and storage in this organ. Net proton secretion is crucial to maintain the acidity of the luminal fluid in the epididymis. A sub-population of epithelial cells, the clear cells, express high levels of the proton-pumping V-ATPase in their apical membrane and are important contributors to luminal acidification. This review describes selected aspects of V-ATPase regulation in clear cells. The assembly of a particular set of V-ATPase subunit isoforms governs the targeting of the pump to the apical plasma membrane. Regulation of V-ATPase-dependent proton secretion occurs via recycling mechanisms. The bicarbonate-activated adenylyl cyclase is involved in the non-hormonal regulation of V-ATPase recycling, following activation of bicarbonate secretion by principal cells. The V-ATPase is also regulated in a paracrine manner by luminal angiotensin II by activation of the angiotensin II type 2 receptor (AGTR2), which is located in basal cells. Basal cells have the remarkable property of extending long and slender cytoplasmic projections that cross the tight junction barrier to monitor the luminal environment. Clear cells are activated by a nitric oxide signal that originates from basal cells. Thus, a complex interplay between the different cell types present in the epithelium leads to activation of the luminal acidifying capacity of the epididymis, a process that is crucial for sperm maturation and storage.
在附睾中,精子获得运动能力和使卵子受精的能力。管腔酸性pH值和低碳酸氢盐浓度有助于精子在该器官成熟和储存期间保持静止状态。净质子分泌对于维持附睾管腔液的酸性至关重要。上皮细胞的一个亚群,即透明细胞,在其顶端膜中表达高水平的质子泵V-ATP酶,是管腔酸化的重要贡献者。本综述描述了透明细胞中V-ATP酶调节的选定方面。一组特定的V-ATP酶亚基异构体的组装决定了该泵靶向顶端质膜。V-ATP酶依赖性质子分泌的调节通过循环机制发生。在主细胞激活碳酸氢盐分泌后,碳酸氢盐激活的腺苷酸环化酶参与V-ATP酶循环的非激素调节。V-ATP酶也通过位于基底细胞中的2型血管紧张素II受体(AGTR2)被管腔血管紧张素II以旁分泌方式调节。基底细胞具有延伸穿过紧密连接屏障以监测管腔环境的长而细的细胞质突起的显著特性。透明细胞被源自基底细胞的一氧化氮信号激活。因此,上皮中存在的不同细胞类型之间的复杂相互作用导致附睾管腔酸化能力的激活,这一过程对精子成熟和储存至关重要。