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PMID:25486458
| Citation |
Zhang, H, Chen, Y, Wadham, C, McCaughan, GW, Keane, FM and Gorrell, MD (2015) Dipeptidyl peptidase 9 subcellular localization and a role in cell adhesion involving focal adhesion kinase and paxillin. Biochim. Biophys. Acta 1853:470-80 |
|---|---|
| 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. |
| Links |
PubMed Online version:10.1016/j.bbamcr.2014.11.029 |
| Keywords |
Antigens, CD29/metabolism; Cell Adhesion/drug effects; Cell Line, Tumor; Cell Membrane/drug effects; Cell Membrane/metabolism; Cell Movement/drug effects; Collagen/pharmacology; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/antagonists & inhibitors; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/metabolism; Down-Regulation/drug effects; EGF Family of Proteins/pharmacology; Fibronectins/pharmacology; Focal Adhesion Protein-Tyrosine Kinases/metabolism; Focal Adhesions/drug effects; Focal Adhesions/metabolism; Humans; Microtubules/drug effects; Microtubules/metabolism; Paxillin/metabolism; Phosphorylation/drug effects; Subcellular Fractions/drug effects; Subcellular Fractions/metabolism; Talin/metabolism; Tetradecanoylphorbol Acetate/pharmacology |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0005874: microtubule |
ECO:0000314: |
C |
Figure 1 D shows microtubule florescence (red), GFP florescence of DPP9 (green), and an overlay of these images in which yellow florescence shows overlapping. This yellow florescence shows that DPP9 is present in the microtubules. |
complete | ||||
| GO:0031252: cell leading edge |
ECO:0000314: |
C |
Figure 3 shows localization of DPP9 near the plasma membrane of the cell leading edge during cell migration. Figure 2 shows that DPP9 is only localized near the plasma membrane and not " physically situated in or on the membrane (Fig. 2D)" |
complete | ||||
Notes
See also
References
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