Cui Mingxue, Fay David S, Han Min
Howard Hughes Medical Institute and Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA.
Genetics. 2004 Jul;167(3):1177-85. doi: 10.1534/genetics.103.024554.
Null mutations in lin-35, the Caenorhabditis elegans ortholog of the mammalian Rb protein, cause no obvious morphological defects. Using a genetic approach to identify genes that may function redundantly with lin-35, we have isolated a mutation in the C. elegans psa-1 gene. lin-35; psa-1 double mutants display severe developmental defects leading to early larval arrest and adult sterility. The psa-1 gene has previously been shown to encode a C. elegans homolog of yeast SWI3, a critical component of the SWI/SNF complex, and has been shown to regulate asymmetric cell divisions during C. elegans development. We observed strong genetic interactions between psa-1 and lin-35 as well as a subset of the class B synMuv genes that include lin-37 and lin-9. Loss-of-function mutations in lin-35, lin-37, and lin-9 strongly enhanced the defects of asymmetric T cell division associated with a psa-1 mutation. Our results suggest that LIN-35/Rb and a certain class B synMuv proteins collaborate with the SWI/SNF protein complex to regulate the T cell division as well as other events essential for larval growth.
线虫(Caenorhabditis elegans)中与哺乳动物Rb蛋白直系同源的lin-35基因发生无效突变时,不会导致明显的形态缺陷。我们采用遗传学方法来鉴定可能与lin-35发挥冗余功能的基因,分离出了线虫psa-1基因的一个突变。lin-35;psa-1双突变体表现出严重的发育缺陷,导致幼虫早期发育停滞和成虫不育。先前的研究表明,psa-1基因编码酵母SWI3的线虫同源物,而酵母SWI3是SWI/SNF复合物的关键组成部分,并且已证明psa-1基因在秀丽隐杆线虫发育过程中调节不对称细胞分裂。我们观察到psa-1与lin-35以及包括lin-37和lin-9在内的B类synMuv基因的一个子集之间存在强烈的遗传相互作用。lin-35、lin-37和lin-9的功能丧失突变强烈增强了与psa-1突变相关的不对称T细胞分裂缺陷。我们的结果表明,LIN-35/Rb和某些B类synMuv蛋白与SWI/SNF蛋白复合物协同作用,以调节T细胞分裂以及幼虫生长所必需的其他事件。