Junctional adhesion molecule A (JAM-A) (JAM-A)

Junctional adhesion molecule A (JAM-A) is a type I transmembrane glycoprotein of the immunoglobulin superfamily localized at cell–cell contacts, especially tight junctions of epithelial and endothelial cells, and is also expressed on leukocytes and platelets. It has two extracellular Ig-like domains, a single transmembrane segment, and a short cytoplasmic tail with phosphorylation sites and a C-terminal PDZ-binding motif that recruits scaffolding proteins such as Afadin and PDZ-GEFs. JAM-A forms cis-homodimers via its N-terminal Ig domain using an R(V/I/L)E motif, and this dimerization underlies adhesive function and outside-in signaling. Functionally, JAM-A regulates tight junction assembly and paracellular permeability, coordinates cell migration by activating Rap1 and modulating β1 integrin, and mediates leukocyte–endothelial interactions through binding to integrins LFA-1, Mac-1, and α4β1. Human JAM-A (hJAM1) also serves as a receptor for reovirus via the viral σ1 attachment protein. Dysregulation of JAM-A has been implicated in inflammatory and cardiovascular diseases, barrier dysfunction, infection, and cancer, making it a potential therapeutic target.

Other names

F11 receptor (F11R)Junctional adhesion molecule 1 (JAM-1)CD321JAMJAM1/hJAM1 (human nomenclature variants in structural literature)

Blocking JAM-A homodimerization to modulate cell migration/adhesion and β1 integrin levels (shown using dimerization-defective mutants and dimerization-blocking antibodies in cells) Inhibiting JAM-A–integrin interactions to affect leukocyte adhesion/transmigration (conceptual, based on JAM–integrin binding) Antagonizing viral attachment by preventing σ1–JAM-A binding (reovirus)