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 i...

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Bibliographic Details
Published in:Experimental cell research 2006-10, Vol.312 (17), p.3298-3311
Main Authors: Orlando, Kelly A., Pittman, Randall N.
Format: Article
Language:English
Subjects:
Acetylglucosamine - metabolism
Amides - pharmacology
Animals
Apoptosis
Apoptosis - physiology
Apoptotic body
Cell Membrane - metabolism
Cell Membrane - ultrastructure
Cells
Enzyme Inhibitors - pharmacology
Execution
Fragmentation
Gene expression
GlcNAc
Golgi
Golgi Apparatus - metabolism
Golgi Apparatus - ultrastructure
Intracellular Signaling Peptides and Proteins - physiology
Kinases
PC12
PC12 Cells
Phagocytosis
Phagocytosis - physiology
Protein-Serine-Threonine Kinases - physiology
Pyridines - pharmacology
Rats
Rho kinase
rho-Associated Kinases
ROCK
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Summary: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.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2006.06.033