Les junctions serrées : Plate-forme de régulation de la prolifération et de la polarité cellulaires

Abstract

Les jonctions serrées scellent les cellules épithéliales et endothéliales entre elles. Elles ont été longtemps considérées comme de simples barrières séparant les deux compartiments membranaires apical et basolatéral, dont la composition en protéines et lipides est différente. De récentes études montrent que diverses proteins impliquées dans la transduction de signaux et le trafic membranaire sont associées aux junctions serrées. Ces dernières servent de lieu d’intégration et de transmission de signaux nécessaires à la régulation de leur assemblage et à la polarization cellulaire, mais aussi à la modulation de l’expression des gènes requise pour la proliferation et la différenciation cellulaires.

Tight junctions (TJ) are specialized plasma membrane microdomains that encircle the apical pole of each epithelial and endothelial cell, separating apical from basolateral side. They form an intercellular diffusion barrier (or gate) regulating the passage of ions, water, and various macromolecules through the paracellular spaces, and a fence restricting the apical/basolateral diffusion of membrane proteins and lipids. This latter function is deeply involved in cancer cell biology, in terms of loss of cell polarity. Several TJ proteins are involved in organizing signal transduction at TJ. For example, the interaction of TJ protein ZO-1 (zonula occludens 1) with the transcription factor ZONAB (ZO-1 associated nucleic acid protein) is important in the regulation of expression of the proto-oncogene Erb-2 as well as epithelial proliferation/differentiation. Recent studies indicate that different proteins involved in membrane trafficking are associated with tight junctions. Among these proteins are the small G-proteins of the Rab family that regulate specific membrane transport events in both endocytic and exocytic pathways. Rab proteins may coordinate the recruitment of protein complexes necessary for the establishment-maintenance of cell polarity. Based on the studies reviewed here, tight junctions emerge as a platform used to coordinate and regulate cell polarity, and proliferation/differentiation.