JAM Family and Related Proteins in Leukocyte Migration (Vestweber Series)

Abstract

Abstract-Exploring the role of junctional adhesion molecules (JAMs) has proven to be varied and controversial. The purpose of this review is to discuss the new and exciting roles of these IgSF molecules and how they have evolved to contribute to diverse functions from development to inflammation. In particular, recent research has focused on JAM subfamily members JAM-A, -B, and -C with newly described roles in leukocyte trafficking during inflammation and angiogenesis. However, research on all JAM family members has demonstrated recurring themes with striking similarities in the many diverse processes they are now known to regulate. (Arterioscler Thromb Vasc Biol. 2007;27:2104-2112.)

Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM-2, JAM-A, and PECAM-1

“…26,35,36 Such a cascade of events is supported by data presented here demonstrating that blockers of both Mac-1 and JAM-C can suppress leukocyte transmigration elicited by TNF-␣, some in agreement with previous studies. 20 Of importance, as the precise mechanism of action of JAM-C in mediating leukocyte transmigration remains unclear, 20,37 eg, it is unclear to what extent JAM-Cmediated leukocyte transmigration in vivo is mediated through its interactions with Mac-1 and/or JAM-B, 37,38 details of the components and cascade of molecular events that mediate leukocyte transmigration as elicited by TNF-␣ require further investigations. Collectively, the present results do, however, provide direct in vivo evidence to indicate that activation of EC and leukocyte TNF-␣ receptors may act in sequence to mediate leukocyte firm adhesion and transmigration, respectively ( Figure 6A).…”

Distinct molecular composition of blood and lymphatic vascular endothelial cell junctions establishes specific functional barriers within the peripheral lymph node

“…In contrast to the members of the claudin-family and occludin, cell junctions of HEV harbor all members of the JAM-family, namely JAM-A, -B and -C and the related member ESAM-1. The JAM have been suggested to contribute to the maintenance of established tight junctions (summarized in [27]) and to mediate immune cell diapedesis across endothelial cells. The precise mechanisms of JAM-mediated immune cell diapedesis across the endothelium remains to be defined, as all JAM can undergo homophilic but also heterophilic interactions with leukocyte integrins.…”

Regulation of testicular tight junctions by gonadotrophins in the adult Djungarian hamster in vivo

“…Together, these data suggest a novel role for JAM-A in spermatogenesis. In other tissues, JAM-A is involved in the movement of cells through epithelial and endothelial tissues, particularly leukocyte migration (for reviews see Bradfield et al 2007). It is believed that this action is achieved by the interactions of JAM-A with various intracellular binding partners (such as partitioning defective proteins PAR3/ PAR6 and RAP-1) to affect cytoskeletal reorganisation (for reviews see Bos 2005, Mandell et al 2005.…”