Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
Autophagy. 2010 Nov;6(8):1192-3. doi: 10.4161/auto.6.8.13474. Epub 2010 Nov 16.
Autophagy is a process to degrade and recycle cytoplasmic contents. Autophagy is required for survival in response to starvation, but has also been associated with cell death. How autophagy functions during cell survival in some contexts and cell death in others is unknown. Drosophila larval salivary glands undergo programmed cell death requiring autophagy genes, and are cleared in the absence of known phagocytosis. Recently, we demonstrated that Draper (Drpr), the Drosophila homolog of C. elegans engulfment receptor CED-1, is required for autophagy induction: during cell death, but not during cell survival. drpr mutants fail to clear salivary glands. drpr knockdown in salivary glands prevents the induction of autophagy, and Atg1 misexpression in drpr null mutants suppresses salivary gland persistence. Surprisingly, drpr knockdown cell-autonomously prevents autophagy induction in dying salivary gland cells, but not in larval fat body cells following starvation. This is the first engulfment factor shown to function in cellular self-clearance, and the first report of a cell-death-specific autophagy regulator.
自噬是一种降解和回收细胞质内容物的过程。自噬是在饥饿时生存所必需的,但也与细胞死亡有关。自噬在某些情况下如何促进细胞存活,而在其他情况下又如何导致细胞死亡,目前尚不清楚。果蝇幼虫唾液腺经历程序性细胞死亡,需要自噬基因,并在缺乏已知吞噬作用的情况下被清除。最近,我们证明了果蝇吞噬受体 CED-1 的同源物 Draper (Drpr) 在自噬诱导中是必需的:在细胞死亡期间,但不在细胞存活期间。drpr 突变体不能清除唾液腺。在唾液腺中敲低 drpr 会阻止自噬的诱导,并且在 drpr 缺失突变体中过表达 Atg1 可以抑制唾液腺的持续存在。令人惊讶的是,drpr 敲低会在垂死的唾液腺细胞中自主地阻止自噬的诱导,但不会在饥饿后的幼虫脂肪体细胞中阻止自噬的诱导。这是第一个被证明在细胞自我清除中起作用的吞噬因子,也是第一个报道的细胞死亡特异性自噬调节剂。