Cabello J, Sämann J, Gómez-Orte E, Erazo T, Coppa A, Pujol A, Büssing I, Schulze B, Lizcano J M, Ferrer I, Baumeister R, Dalfo E
CIBIR (Centre for Biomedical Research of La Rioja), C/Piqueras 98, Logroño 26006, Spain.
Bioinformatics and Molecular Genetics (Faculty of Biology), Center for Biochemistry and Molecular Cell Research (Faculty of Medicine), Schänzlestrasse 1, Freiburg 79104, Germany.
Cell Death Dis. 2014 Mar 13;5(3):e1120. doi: 10.1038/cddis.2014.57.
Apoptotic cell death is an integral part of cell turnover in many tissues, and proper corpse clearance is vital to maintaining tissue homeostasis in all multicellular organisms. Even in tissues with high cellular turnover, apoptotic cells are rarely seen because of efficient clearance mechanisms in healthy individuals. In Caenorhabditis elegans, two parallel and partly redundant conserved pathways act in cell corpse engulfment. The pathway for cytoskeletal rearrangement requires the small GTPase CED-10 Rac1 acting for an efficient surround of the dead cell. The CED-10 Rac pathway is also required for the proper migration of the distal tip cells (DTCs) during the development of the C. elegans gonad. Parkin, the mammalian homolog of the C. elegans PDR-1, interacts with Rac1 in aged human brain and it is also implicated with actin dynamics and cytoskeletal rearrangements in Parkinsons's disease, suggesting that it might act on engulfment. Our genetic and biochemical studies indicate that PDR-1 inhibits apoptotic cell engulfment and DTC migration by ubiquitylating CED-10 for degradation.
凋亡性细胞死亡是许多组织中细胞更新的一个组成部分，而妥善清除细胞尸体对于所有多细胞生物体维持组织稳态至关重要。即使在细胞更新率高的组织中，由于健康个体中存在有效的清除机制，凋亡细胞也很少见。在秀丽隐杆线虫中，两条平行且部分冗余的保守途径参与细胞尸体吞噬。细胞骨架重排途径需要小GTP酶CED-10 Rac1发挥作用，以有效地包围死亡细胞。CED-10 Rac途径在秀丽隐杆线虫性腺发育过程中对于远端末梢细胞（DTC）的正常迁移也是必需的。线虫PDR-1的哺乳动物同源物Parkin在老年人类大脑中与Rac1相互作用，并且在帕金森病中也与肌动蛋白动力学和细胞骨架重排有关，这表明它可能作用于吞噬过程。我们的遗传学和生物化学研究表明，PDR-1通过泛素化CED-10使其降解来抑制凋亡细胞的吞噬和DTC迁移。
