title: Dipeptidyl peptidase 9 subcellular localization and a role in cell adhesion involving focal adhesion kinase and paxillin.
abstract: Dipeptidyl peptidase 9 (DPP9) is a ubiquitously expressed member of the DPP4 gene and protease family. Deciphering the biological functions of DPP9 and its roles in pathogenesis has implicated DPP9 in tumor biology, the immune response, apoptosis, intracellular epidermal growth factor-dependent signaling and cell adhesion and migration. We investigated the intracellular distribution of DPP9 chimeric fluorescent proteins and consequent functions of DPP9. We showed that while some DPP9 is associated with mitochondria, the strongest co-localization was with microtubules. Under steady state conditions, DPP9 was not seen at the plasma membrane, but upon stimulation with either phorbol 12-myristate 13-acetate or epidermal growth factor, some DPP9 re-distributed towards the ruffling membrane. DPP9 was seen at the leading edge of the migrating cell and co-localized with the focal adhesion proteins, integrin-β1 and talin. DPP9 gene silencing and treatment with a DPP8/DPP9 specific inhibitor both reduced cell adhesion and migration. Expression of integrin-β1 and talin was decreased in DPP9-deficient and DPP9-enzyme-inactive cells. There was a concomitant decrease in the phosphorylation of focal adhesion kinase and paxillin, indicating that DPP9 knockdown or enzyme inhibition suppressed the associated adhesion signaling pathway, causing impaired cell movement. These novel findings provide mechanistic insights into the regulatory role of DPP9 in cell movement, and may thus implicate DPP9 in tissue and tumor growth and metastasis.
authors.affiliation: Centenary Institute and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Centenary Institute and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Yiqian
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Centenary Institute and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Carol
authors.initials: C
authors.lastname: Wadham
authors.affiliation: Centenary Institute and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: McCaughan
authors.affiliation: Centenary Institute and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Keane
authors.affiliation: Centenary Institute and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. Electronic address: m.gorrell@centenary.usyd.edu.au.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Gorrell
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D066255:EGF Family of Proteins / Q000494:pharmacology; D005353:Fibronectins / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D051419:Paxillin / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D016608:Talin / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D066255:EGF Family of Proteins; D005353:Fibronectins; D019012:Integrin beta1; D051419:Paxillin; D016608:Talin; D003094:Collagen; D051416:Focal Adhesion Protein-Tyrosine Kinases; C471241:DPP9 protein, human; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D013755:Tetradecanoylphorbol Acetate
keywords: Dipeptidyl peptidase; Focal adhesion; Localization; Migration