PKCε-mediated phosphorylation of vimentin controls integrin recycling and motility

Johanna Ivaska, Karoliina Vuoriluoto, Tuomas Huovinen, Ichiro Izawa, Masaki Inagaki, Peter J. Parker (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

PKCε controls the transport of endocytosed β1-integrins to the plasma membrane regulating directional cell motility. Vimentin, an intermediate filament protein upregulated upon epithelial cell transformation, is shown here to be a proximal PKCε target within the recycling integrin compartment. On inhibition of PKC and vimentin phosphorylation, integrins become trapped in vesicles and directional cell motility towards matrix is severely attenuated. In vitro reconstitution assays showed that PKCε dissociates from integrin containing endocytic vesicles in a selectively phosphorylated vimentin containing complex. Mutagenesis of PKC (controlled) sites on vimentin and ectopic expression of the variant leads to the accumulation of intracellular PKCε/integrin positive vesicles. Finally, introduction of ectopic wild‐type vimentin is shown to promote cell motility in a PKCε-dependent manner; alanine substitutions in PKC (controlled) sites on vimentin abolishes the ability of vimentin to induce cell migration, whereas the substitution of these sites with acidic residues enables vimentin to rescue motility of PKCε null cells. Our results indicate that PKC‐mediated phosphorylation of vimentin is a key process in integrin traffic through the cell.
Original languageEnglish
Pages (from-to)3834-3845
JournalEMBO Journal
Volume24
Issue number22
DOIs
Publication statusPublished - 2005
MoE publication typeA1 Journal article-refereed

Fingerprint

Phosphorylation
Recycling
Vimentin
Integrins
Cell Movement
Substitution reactions
Intermediate Filament Proteins
Transport Vesicles
Null Lymphocytes
Mutagenesis
Cell membranes
Endocytosis
Alanine
Assays
Epithelial Cells
Cell Membrane

Keywords

  • integrin
  • intermediate filament
  • migration
  • PKC
  • vimentin

Cite this

Ivaska, J., Vuoriluoto, K., Huovinen, T., Izawa, I., Inagaki, M., & Parker, P. J. (2005). PKCε-mediated phosphorylation of vimentin controls integrin recycling and motility. EMBO Journal, 24(22), 3834-3845. https://doi.org/10.1038/sj.emboj.7600847
Ivaska, Johanna ; Vuoriluoto, Karoliina ; Huovinen, Tuomas ; Izawa, Ichiro ; Inagaki, Masaki ; Parker, Peter J. / PKCε-mediated phosphorylation of vimentin controls integrin recycling and motility. In: EMBO Journal. 2005 ; Vol. 24, No. 22. pp. 3834-3845.
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Ivaska, J, Vuoriluoto, K, Huovinen, T, Izawa, I, Inagaki, M & Parker, PJ 2005, 'PKCε-mediated phosphorylation of vimentin controls integrin recycling and motility', EMBO Journal, vol. 24, no. 22, pp. 3834-3845. https://doi.org/10.1038/sj.emboj.7600847

PKCε-mediated phosphorylation of vimentin controls integrin recycling and motility. / Ivaska, Johanna; Vuoriluoto, Karoliina; Huovinen, Tuomas; Izawa, Ichiro; Inagaki, Masaki; Parker, Peter J. (Corresponding Author).

In: EMBO Journal, Vol. 24, No. 22, 2005, p. 3834-3845.

Research output: Contribution to journalArticleScientificpeer-review

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AB - PKCε controls the transport of endocytosed β1-integrins to the plasma membrane regulating directional cell motility. Vimentin, an intermediate filament protein upregulated upon epithelial cell transformation, is shown here to be a proximal PKCε target within the recycling integrin compartment. On inhibition of PKC and vimentin phosphorylation, integrins become trapped in vesicles and directional cell motility towards matrix is severely attenuated. In vitro reconstitution assays showed that PKCε dissociates from integrin containing endocytic vesicles in a selectively phosphorylated vimentin containing complex. Mutagenesis of PKC (controlled) sites on vimentin and ectopic expression of the variant leads to the accumulation of intracellular PKCε/integrin positive vesicles. Finally, introduction of ectopic wild‐type vimentin is shown to promote cell motility in a PKCε-dependent manner; alanine substitutions in PKC (controlled) sites on vimentin abolishes the ability of vimentin to induce cell migration, whereas the substitution of these sites with acidic residues enables vimentin to rescue motility of PKCε null cells. Our results indicate that PKC‐mediated phosphorylation of vimentin is a key process in integrin traffic through the cell.

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Ivaska J, Vuoriluoto K, Huovinen T, Izawa I, Inagaki M, Parker PJ. PKCε-mediated phosphorylation of vimentin controls integrin recycling and motility. EMBO Journal. 2005;24(22):3834-3845. https://doi.org/10.1038/sj.emboj.7600847