PDK1 regulates focal adhesion disassembly by modulating endocytosis of αvβ3 integrin

Laura di Blasio, Paolo Armando Gagliardi, Alberto Puliafito, Roberto Sessa, Giorgio Seano, Federico Bussolino, Luca Primo

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Non-amoeboid cell migration is characterised by dynamic competition among multiple protrusions to establish new adhesion sites at the cell's leading edge. However, the mechanisms that regulate the decision to disassemble or to grow nascent adhesions are not fully understood. Here we show that, in endothelial cells, 3- phosphoinositide-dependent protein kinase 1 (PDK1) promotes focal adhesion (FA) turnover by controlling endocytosis of integrin αvβ3 in a PI3K-dependent manner. We demonstrate that PDK1 binds and phosphorylates integrin αvβ3. Downregulation of PDK1 increases FA size and slows down their disassembly. This process requires both PDK1 kinase activity and PI3K activation but does not involve Akt. Moreover, PDK1 silencing stabilises FA in membrane protrusions decreasing migration of endothelial cells on vitronectin. These results indicate that modulation of integrin endocytosis by PDK1 hampers endothelial cell adhesion and migration on extracellular matrix, thus unveiling a novel role for this kinase.

Original languageEnglish
Pages (from-to)863-877
Number of pages15
JournalJournal of Cell Science
Volume128
Issue number5
DOIs
Publication statusPublished - 2015

Fingerprint

Focal Adhesions
Phosphatidylinositols
Endocytosis
Integrins
Protein Kinases
Endothelial Cells
Phosphatidylinositol 3-Kinases
Cell Movement
3-Phosphoinositide-Dependent Protein Kinases
Phosphotransferases
Vitronectin
Cell Adhesion
Extracellular Matrix
Down-Regulation
Membranes

Keywords

  • Endothelial cells
  • Focal adhesion
  • Integrin endocytosis
  • PDK1
  • PI3K

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

PDK1 regulates focal adhesion disassembly by modulating endocytosis of αvβ3 integrin. / di Blasio, Laura; Gagliardi, Paolo Armando; Puliafito, Alberto; Sessa, Roberto; Seano, Giorgio; Bussolino, Federico; Primo, Luca.

In: Journal of Cell Science, Vol. 128, No. 5, 2015, p. 863-877.

Research output: Contribution to journalArticle

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AU - Seano, Giorgio

AU - Bussolino, Federico

AU - Primo, Luca

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AB - Non-amoeboid cell migration is characterised by dynamic competition among multiple protrusions to establish new adhesion sites at the cell's leading edge. However, the mechanisms that regulate the decision to disassemble or to grow nascent adhesions are not fully understood. Here we show that, in endothelial cells, 3- phosphoinositide-dependent protein kinase 1 (PDK1) promotes focal adhesion (FA) turnover by controlling endocytosis of integrin αvβ3 in a PI3K-dependent manner. We demonstrate that PDK1 binds and phosphorylates integrin αvβ3. Downregulation of PDK1 increases FA size and slows down their disassembly. This process requires both PDK1 kinase activity and PI3K activation but does not involve Akt. Moreover, PDK1 silencing stabilises FA in membrane protrusions decreasing migration of endothelial cells on vitronectin. These results indicate that modulation of integrin endocytosis by PDK1 hampers endothelial cell adhesion and migration on extracellular matrix, thus unveiling a novel role for this kinase.

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