The role of EFA6, exchange factor for Arf6, for tight junction assembly, functions, and interaction with the actin cytoskeleton.
In polarized epithelial cells, the tight junction has been ascribed several functions including the regulation of the paracellular permeability, an impediment to the diffusion of molecules between the apical and basolateral domains, a site of delivery of transport vesicles for basolateral proteins, and a scaffold for structural and signaling molecules. The tight junction is anchored physically into the apical actin cytoskeleton circumscribing the cell, which is known as the perijunctional actomyosin ring. This connection was first suggested by experiments using the actin depolymerizing drug cytochalasin, which was also found to disrupt the transepithelial permeability. Since then a large number of studies have reported the effects of drugs, molecular tools, or physiological and pathological conditions that alter coordinately actin organization and the tight junction. In support of this model, proteins of the tight junction, such as the members of the ZO family and occludin, have been shown to bind to actin. However, very little is known regarding the molecular mechanisms by which the actin cytoskeleton modulates tight junction functions. We have studied the role of the Exchange Factor for Arf6, EFA6, in tight junction assembly. By combining a large panel of methods, including morphological, physiological, and biochemical, described in detail hereafter we demonstrated that EFA6 plays a role in the physical association of the tight junction to the perijunctional actomyosin ring.
Luton
Frédéric
F
Institut de Pharmacologie, Moléculaire et Cellulaire, CNRS, Valbonne Sophia-Antipolis, France.
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000502:physiology*; D000199:Actins / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D003902:Detergents; D004285:Dogs; D004705:Endocytosis; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010539:Permeability / Q000187:drug effects; D012995:Solubility; D019108:Tight Junctions / Q000187:drug effects / Q000502:physiology*
D000089982:ADP-Ribosylation Factor 6; D000199:Actins; D003902:Detergents; D020662:Guanine Nucleotide Exchange Factors; D020727:ADP-Ribosylation Factors