Vaughan Emily M, You Jae-Sung, Elsie Yu Hoi-Ying, Lasek Amber, Vitale Nicolas, Hornberger Troy A, Bement William M
Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706Department of Zoology, University of Wisconsin-Madison, Madison, WI 53706.
Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53706.
Mol Biol Cell. 2014 Jun 15;25(12):1867-76. doi: 10.1091/mbc.E14-03-0839. Epub 2014 Apr 30.
After damage, cells reseal their plasma membrane and repair the underlying cortical cytoskeleton. Although many different proteins have been implicated in cell repair, the potential role of specific lipids has not been explored. Here we report that cell damage elicits rapid formation of spatially organized lipid domains around the damage site, with different lipids concentrated in different domains as a result of both de novo synthesis and transport. One of these lipids-diacylglycerol (DAG)-rapidly accumulates in a broad domain that overlaps the zones of active Rho and Cdc42, GTPases that regulate repair of the cortical cytoskeleton. Formation of the DAG domain is required for Cdc42 and Rho activation and healing. Two DAG targets, protein kinase C (PKC) β and η, are recruited to cell wounds and play mutually antagonistic roles in the healing process: PKCβ participates in Rho and Cdc42 activation, whereas PKCη inhibits Rho and Cdc42 activation. The results reveal an unexpected diversity in subcellular lipid domains and the importance of such domains for a basic cellular process.
细胞受损后会重新封闭其质膜并修复下方的皮质细胞骨架。尽管许多不同的蛋白质都与细胞修复有关，但特定脂质的潜在作用尚未得到探索。在此我们报告，细胞损伤会引发损伤部位周围空间组织化脂质结构域的快速形成，由于从头合成和转运，不同的脂质集中在不同的结构域中。其中一种脂质——二酰基甘油（DAG）——迅速在一个广泛的结构域中积累，该结构域与调节皮质细胞骨架修复的活性Rho和Cdc42小G蛋白的区域重叠。DAG结构域的形成是Cdc42和Rho激活及愈合所必需的。两个DAG靶点，蛋白激酶C（PKC）β和η，被招募到细胞伤口处，并在愈合过程中发挥相互拮抗的作用：PKCβ参与Rho和Cdc42的激活，而PKCη抑制Rho和Cdc42的激活。这些结果揭示了亚细胞脂质结构域中意想不到的多样性以及此类结构域对基本细胞过程的重要性。
