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CLIC4 regulates cell adhesion and β1 integrin trafficking

Elisabetta Argenzio1, Coert Margadant2, Daniela Leyton-Puig2

  • 1Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands e.argenzio@nki.nl w.moolenaar@nki.nl.

Journal of Cell Science
|October 26, 2014
PubMed

Insights

Chloride intracellular channel protein 4 (CLIC4) regulates cell adhesion and motility by controlling β1 integrin trafficking. This protein suppresses Rab35 activity, impacting cell movement and signaling pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Chloride intracellular channel protein 4 (CLIC4) has diverse cellular roles, including ion channel formation and membrane remodeling.
  • CLIC4's recruitment to the plasma membrane by lysophosphatidic acid (LPA) and serum suggests involvement in exocytic-endocytic trafficking, but its precise function and targets are unclear.

Purpose of the Study:

  • To elucidate the function and subcellular targets of CLIC4 in cellular processes.
  • To investigate CLIC4's role in integrin trafficking and its relationship with Rab35.

Main Methods:

  • CLIC4 knockdown in HeLa and MDA-MB-231 cells.
  • Analysis of cell-matrix adhesion, cell spreading, cell motility, and integrin signaling.
  • Immunofluorescence microscopy to track CLIC4 and β1 integrin localization.
  • Assessment of β1 integrin internalization and recycling.
  • Investigation of CLIC4's effect on Rab35 activity.

Main Results:

  • CLIC4 knockdown reduced cell-matrix adhesion, cell spreading, and integrin signaling, while increasing cell motility.
  • LPA stimulated CLIC4 recruitment to β1 integrin at the plasma membrane and in Rab35-positive endosomes.
  • CLIC4 is essential for β1 integrin internalization and recycling, but not for EGF receptor trafficking.
  • CLIC4 suppresses Rab35 activity, antagonizing Rab35-dependent β1 integrin trafficking.

Conclusions:

  • CLIC4 regulates cell adhesion, spreading, and motility.
  • CLIC4 is a key regulator of β1 integrin trafficking, controlling its internalization and recycling.
  • CLIC4 acts as a suppressor of Rab35 activity, thereby influencing integrin-mediated cellular processes.
Keywords:
CLIC4Cell adhesionIntegrin traffickingLysophosphatidic acidRab35

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