title: Rac1 GTPase acts downstream of αPS1βPS integrin to control collective migration and lumen size in the Drosophila salivary gland.
abstract: During collective migration of the Drosophila embryonic salivary gland, the distal gland cells mediate integrin-based contacts with surrounding tissues while proximal gland cells change shape and rearrange. Here, we show that αPS1βPS integrin controls salivary gland migration through Rac1 GTPase which downregulates E-cadherin in proximal and distal gland cells, and promotes extension of actin-rich basal membrane protrusions in the distal cells. In embryos mutant for multiple edematous wings (mew), which encodes the αPS1 subunit of the αPS1βPS integrin heterodimer, or rac1 and rac2 GTPases, salivary gland cells failed to migrate, to downregulate E-cadherin and to extend basal membrane protrusions. Selective inhibition of Rac1 in just the proximal or distal gland cells demonstrate that proximal gland cells play an active role in the collective migration of the whole gland and that continued migration of the distal cells depends on the proximal cells. Loss of rac1rac2 also affected gland lumen length and width whereas, loss of mew affected lumen length only. Activation of rac1 in mew mutant embryos significantly rescued the gland migration, lumen length and basal membrane protrusion defects and partially rescued the E-cadherin defects. Independent of mew, Rac regulates cell shape change and rearrangement in the proximal gland, which is important for migration and lumen width. Our studies shed novel insight into a Rac1-mediated link between integrin and cadherin adhesion proteins in vivo, control of lumen length and width and how activities of proximal and distal gland cells are coordinated to result in the collective migration of the entire salivary gland.
authors.affiliation: Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Pirraglia
authors.forename: Jenna
authors.initials: J
authors.lastname: Walters
authors.forename: Nancy
authors.initials: N
authors.lastname: Ahn
authors.forename: Monn Monn
authors.initials: MM
authors.lastname: Myat
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement; D048430:Cell Shape; D022081:Cell Surface Extensions / Q000378:metabolism; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000166:cytology* / Q000196:embryology / Q000201:enzymology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D039001:Integrin alpha Chains / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009929:Organ Size; D012469:Salivary Glands / Q000033:anatomy & histology / Q000166:cytology* / Q000201:enzymology; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D015820:Cadherins; D029721:Drosophila Proteins; D039001:Integrin alpha Chains; D016023:Integrins; C090146:Rac1 protein, Drosophila; C082188:if protein, Drosophila; C511153:Rho1 protein, Drosophila; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins