Rho kinase regulates phagocytosis, surface expression of GlcNAc, and Golgi fragmentation of apoptotic PC12 cells.
Apoptotic cells undergo a number of changes to prepare for phagocytosis; most occur during the execution phase of apoptosis, when dying cells undergo shrinkage and/or fragmentation into apoptotic bodies and express phagocytic markers on their surface. Although events during the execution phase are important to prepare corpses for phagocytosis, the mechanisms that control most execution phase events are unknown. To understand regulation of execution events we focused on Rho kinase (ROCK), because one isoform of ROCK, ROCK-I, is constitutively activated by caspases during execution. Using apoptotic PC12 cells as a model, we find that inhibition of ROCK activity during apoptosis decreases surface expression of GlcNAc, a carbohydrate known to function as a phagocytic marker. In addition, inhibition of ROCK blocks Golgi fragmentation in apoptotic cells, and constitutively active ROCK induces Golgi fragmentation in the absence of apoptosis. Importantly, PC12 cells dying in the presence of a ROCK inhibitor are less efficiently phagocytized than those dying without the inhibitor. These data highlight the role of ROCK in multiple processes in the execution phase of apoptosis, and suggest that ROCK plays an important role in controlling the outcome of apoptosis, that is, preparation of corpses for phagocytosis.
Orlando
Kelly A
KA
Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Pittman
Randall N
RN
D000117:Acetylglucosamine / Q000378:metabolism*; D000577:Amides / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D016716:PC12 Cells; D010587:Phagocytosis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D054460:rho-Associated Kinases
D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D000117:Acetylglucosamine