title: Polarization of the epithelial layer and apical localization of integrins are required for engulfment of apoptotic cells in the Drosophila ovary.
abstract: Inefficient clearance of dead cells or debris by epithelial cells can lead to or exacerbate debilitating conditions such as retinitis pigmentosa, macular degeneration, chronic obstructive pulmonary disease and asthma. Despite the importance of engulfment by epithelial cells, little is known about the molecular changes that are required within these cells. The misregulation of integrins has previously been associated with disease states, suggesting that a better understanding of the regulation of receptor trafficking could be key to treating diseases caused by defects in phagocytosis. Here, we demonstrate that the integrin heterodimer αPS3/βPS becomes apically enriched and is required for engulfment by the epithelial follicle cells of the Drosophila ovary. We found that integrin heterodimer localization and function is largely directed by the α-subunit. Moreover, proper cell polarity promotes asymmetric integrin enrichment, suggesting that αPS3/βPS trafficking occurs in a polarized fashion. We show that several genes previously known for their roles in trafficking and cell migration are also required for engulfment. Moreover, as in mammals, the same α-integrin subunit is required by professional and non-professional phagocytes and migrating cells in Drosophila. Our findings suggest that migrating and engulfing cells use common machinery, and demonstrate a crucial role for integrin function and polarized trafficking of integrin subunits during engulfment. This study also establishes the epithelial follicle cells of the Drosophila ovary as a powerful model for understanding the molecular changes required for engulfment by a polarized epithelium.
authors.affiliation: Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USA.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Meehan
authors.affiliation: Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Kleinsorge
authors.affiliation: Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USA.
authors.forename: Allison K
authors.initials: AK
authors.lastname: Timmons
authors.affiliation: Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Taylor
authors.affiliation: Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USA kmccall@bu.edu.
authors.forename: Kimberly
authors.initials: K
authors.lastname: McCall
mesh_terms: D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D016764:Cell Polarity; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006056:Golgi Apparatus / Q000378:metabolism; D039001:Integrin alpha Chains / Q000378:metabolism*; D008954:Models, Biological; D006080:Ovarian Follicle / Q000166:cytology; D010053:Ovary / Q000166:cytology*; D010587:Phagocytosis; D055503:Protein Multimerization; D021122:Protein Subunits / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D039001:Integrin alpha Chains; D021122:Protein Subunits; C572269:alpha PS3 integrin, Drosophila; C082188:if protein, Drosophila
keywords: Apoptosis; Drosophila; Epithelial cell; Integrin; Migration; Ovary; Phagocytosis; Polarity