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MarvelD3 couples tight junctions to the MEKK1-JNK pathway to regulate cell behavior and survival

Emily Steed1, Ahmed Elbediwy, Barbara Vacca

  • 1Department of Cell Biology, Institute of Ophthalmology, University College London, London EC1V 9EL, England, UK.

The Journal of Cell Biology
|February 26, 2014
PubMed

Insights

MarvelD3 regulates cell behavior by linking tight junctions to the MEKK1-JNK pathway. This protein controls cell migration, proliferation, and survival, impacting tumor formation.

Area of Science:

  • Cell biology
  • Molecular signaling
  • Cancer research

Background:

  • MarvelD3 is a transmembrane protein in tight junctions, but its role in barrier function and signaling is unclear.
  • Tight junctions regulate cell proliferation, yet the link between junctional components and signaling pathways remains poorly understood.

Purpose of the Study:

  • To investigate MarvelD3's role in regulating cell behavior and signaling pathways.
  • To determine how MarvelD3 influences the MEKK1-c-Jun NH2-terminal kinase (JNK) pathway.

Main Methods:

  • Studied MarvelD3 expression in differentiating Caco-2 cells and a metastatic tumor cell line.
  • Assessed cell migration, proliferation, and in vivo tumor formation.
  • Analyzed MEKK1 recruitment, JNK phosphorylation, and transcriptional activity.

Main Results:

  • Loss of MarvelD3 increased cell migration and proliferation; reexpression inhibited these processes and tumor formation.
  • MarvelD3 expression inversely correlated with JNK activity, as MarvelD3 recruited MEKK1 to junctions, down-regulating JNK.
  • MarvelD3 depletion led to junction dissociation and cell death during osmotic stress.

Conclusions:

  • MarvelD3 dynamically regulates the MEKK1-JNK pathway, impacting cell behavior and survival.
  • MarvelD3 couples tight junctions to signaling, influencing cell migration, proliferation, and tumor growth.

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