Structural determinants of Junctional Adhesion Molecule A (JAM-A) function and mechanisms of intracellular signaling.
Junctional Adhesion Molecule A (JAM-A) is a multifunctional cell surface protein that has multiple evolutionarily conserved structural features. There is now conclusive evidence that discrete structural elements on JAM-A mediate intracellular signaling events that alter cell migration and paracellular permeability. Specifically, self-dimerization between extracellular Ig-like loops and close apposition of PDZ-dependent, JAM-A-associated intracellular scaffold proteins such as Afadin and guanine-nucleotide exchange factors mediate activation of Rap1 and modulation of epithelial cell migration by effects on beta1 integrin. While the same JAM-A structural features also modulate migration of other cell types and paracellular permeability in epithelia/endothelia, additional signaling proteins/mechanisms are probably involved. Recent insights into JAM-A outside-in signaling events that regulate these cellular functions are discussed.
Severson
Eric A
EA
Department of Pathology and Laboratory Medicine, Emory University, 615 Michael Street, Atlanta, GA 30322, USA.
Parkos
Charles A
CA
D000818:Animals; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002465:Cell Movement; D006801:Humans; D042541:Intracellular Space / Q000737:chemistry / Q000378:metabolism*; D062726:Junctional Adhesion Molecules; D015398:Signal Transduction
D015815:Cell Adhesion Molecules; D062726:Junctional Adhesion Molecules