Modulation of tight junction function by G protein-coupled events.
Small G proteins or GTPases comprise a growing family of signal transduction molecules with inducible properties dependent upon reversible interactions with guanine nucleotides. Activation status of the proteins is characterized by preferential affinity for triphosphorylated guanine nucleotides, initiating signaling events that control fundamental processes involved in cell migration and contraction. Termination of small G protein signaling activity is in part achieved through intrinsic GTPase activity, which catalyzes the removal of GTP and its replacement with functionally inactive GDP. Recent investigations have implicated various small G proteins as messengers that control cell-cell contact between scaffold proteins and the actin cytoskeleton, suggesting an intrinsic mechanism for the regulation of paracellular permeability in polarized epithelial and endothelial cells. This review will examine current evidence for the control of tight junction permeability by small G proteins, and speculate upon future directions that may be of value in further exploring the biological importance of these key mediators.
Hopkins
A M
AM
Epithelial Pathobiology Research Unit, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
Li
D
D
Mrsny
R J
RJ
Walsh
S V
SV
Nusrat
A
A
D000818:Animals; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D010539:Permeability; D019108:Tight Junctions / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000502:physiology; D020692:rab3 GTP-Binding Proteins / Q000502:physiology; D018631:ras Proteins / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000502:physiology
D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein; D020692:rab3 GTP-Binding Proteins; D018631:ras Proteins; D020742:rhoA GTP-Binding Protein