Conserved role for autophagy in Rho1-mediated cortical remodeling and blood cell recruitment.
Dynamic regulation of cell shape underlies many developmental and immune functions. Cortical remodeling is achieved under the central control of Rho GTPase pathways that modulate an exquisite balance in the dynamic assembly and disassembly of the cytoskeleton and focal adhesions. Macroautophagy (autophagy), associated with bulk cytoplasmic remodeling through lysosomal degradation, has clearly defined roles in cell survival and death. Moreover, it is becoming apparent that proteins, organelles, and pathogens can be targeted for autophagic clearance by selective mechanisms, although the extent and roles of such degradation are unclear. Here we report a conserved role for autophagy specifically in the cortical remodeling of Drosophila blood cells (hemocytes) and mouse macrophages. Continuous autophagy was required for integrin-mediated hemocyte spreading and Rho1-induced cell protrusions. Consequently, hemocytes disrupted for autophagy were impaired in their recruitment to epidermal wounds. Cell spreading required ref(2)P, the Drosophila p62 multiadaptor, implicating selective autophagy as a novel mechanism for modulating cortical dynamics. These results illuminate a specific and conserved role for autophagy as a regulatory mechanism for cortical remodeling, with implications for immune cell function.
Kadandale
Pavan
P
Section of Cell & Developmental Biology and Departments of Cellular and Molecular Medicine and Medicine, University of California, San Diego, CA 92093, USA.
Stender
Joshua D
JD
Glass
Christopher K
CK
Kiger
Amy A
AA
D000818:Animals; D001343:Autophagy; D000071189:Autophagy-Related Protein-1 Homolog; D002448:Cell Adhesion; D002470:Cell Survival; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D006434:Hemocytes / Q000166:cytology* / Q000201:enzymology*; D008264:Macrophages / Q000166:cytology* / Q000201:enzymology*; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; C518074:Atg1 protein, Drosophila; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C511153:Rho1 protein, Drosophila; D020741:rho GTP-Binding Proteins