title: The secreted AdamTS-A metalloprotease is required for collective cell migration.
abstract: Members of the ADAMTS family of secreted metalloproteases play crucial roles in modulating the extracellular matrix (ECM) in development and disease. Here, we show that ADAMTS-A, the Drosophila ortholog of human ADAMTS 9 and ADAMTS 20, and of C. elegans GON-1, is required for cell migration during embryogenesis. AdamTS-A is expressed in multiple migratory cell types, including hemocytes, caudal visceral mesoderm (CVM), the visceral branch of the trachea (VBs) and the secretory portion of the salivary gland (SG). Loss of AdamTS-A causes defects in germ cell, CVM and VB migration and, depending on the tissue, AdamTS-A functions both autonomously and non-autonomously. In the highly polarized collective of the SG epithelium, loss of AdamTS-A causes apical surface irregularities and cell elongation defects. We provide evidence that ADAMTS-A is secreted into the SG lumen where it functions to release cells from the apical ECM, consistent with the defects observed in AdamTS-A mutant SGs. We show that loss of the apically localized protocadherin Cad99C rescues the SG defects, suggesting that Cad99C serves as a link between the SG apical membrane and the secreted apical ECM component(s) cleaved by ADAMTS-A. Our analysis of AdamTS-A function in the SG suggests a novel role for ADAMTS proteins in detaching cells from the apical ECM, facilitating tube elongation during collective cell migration.
authors.affiliation: Department of Cell Biology, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2196, USA.
authors.forename: Afshan
authors.initials: A
authors.lastname: Ismat
authors.forename: Alan M
authors.initials: AM
authors.lastname: Cheshire
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Andrew
mesh_terms: D051722:ADAM Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D002465:Cell Movement; D016764:Cell Polarity; D048430:Cell Shape; D004331:Drosophila melanogaster / Q000145:classification / Q000166:cytology / Q000196:embryology / Q000201:enzymology*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000201:enzymology; D047108:Embryonic Development; D005109:Extracellular Matrix / Q000201:enzymology; D017344:Genes, Insect; D006434:Hemocytes / Q000201:enzymology; D007150:Immunohistochemistry; D008648:Mesoderm / Q000166:cytology / Q000196:embryology / Q000201:enzymology; D010641:Phenotype; D010802:Phylogeny; D012469:Salivary Glands / Q000166:cytology / Q000201:enzymology; D014132:Trachea / Q000196:embryology / Q000201:enzymology
chemical_list: C512040:Cad99c protein, Drosophila; D015820:Cadherins; D051722:ADAM Proteins
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