Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Curr Biol. 2011 Jun 7;21(11):948-54. doi: 10.1016/j.cub.2011.04.025. Epub 2011 May 19.
During development, all cells make the decision to live or die. Although the molecular mechanisms that execute the apoptotic program are well defined, less is known about how cells decide whether to live or die. In C. elegans, this decision is linked to how cells divide asymmetrically [1, 2]. Several classes of molecules are known to regulate asymmetric cell divisions in metazoans, yet these molecules do not appear to control C. elegans divisions that produce apoptotic cells [3]. We identified CNT-2, an Arf GTPase-activating protein (GAP) of the AGAP family, as a novel regulator of this type of neuroblast division. Loss of CNT-2 alters daughter cell size and causes the apoptotic cell to adopt the fate of its sister cell, resulting in extra neurons. CNT-2's Arf GAP activity is essential for its function in these divisions. The N terminus of CNT-2, which contains a GTPase-like domain that defines the AGAP class of Arf GAPs, negatively regulates CNT-2's function. We provide evidence that CNT-2 regulates receptor-mediated endocytosis and consider the implications of its role in asymmetric cell divisions.
在发育过程中，所有细胞都要做出生存或死亡的决定。尽管执行凋亡程序的分子机制已经得到很好的定义，但对于细胞如何决定生存还是死亡知之甚少。在秀丽隐杆线虫中，这个决定与细胞如何不对称分裂有关[1,2]。已经有几类分子被认为可以调节后生动物的不对称细胞分裂，但这些分子似乎并不控制产生凋亡细胞的秀丽隐杆线虫的分裂[3]。我们鉴定出 CNT-2 是 AGAP 家族的 Arf GTPase 激活蛋白（GAP），它是这种神经母细胞分裂的新型调节因子。CNT-2 的缺失会改变子细胞的大小，并导致凋亡细胞采用其姐妹细胞的命运，从而产生额外的神经元。CNT-2 的 Arf GAP 活性对其在这些分裂中的功能至关重要。CNT-2 的 N 端包含一个 GTPase 样结构域，该结构域定义了 AGAP 类的 Arf GAP，它负调控 CNT-2 的功能。我们提供了证据表明，CNT-2 调节受体介导的内吞作用，并考虑了其在不对称细胞分裂中的作用的影响。
