Junctional Adhesion Molecules (JAMs) - Adhesion Molecules - page 38

formation of tight junctions in epithelial and endothelial cells, the development
of spermatids or the formation of functional nerves. Recent evidence indicates
that JAMs play a role in cell migration and proliferation, suggesting that their
functions are more diverse than anticipated. Here, we will review the role of JAMs
in dif erent biological systems.
INTRODUCTION
Junctional adhesion molecules (JAMs) are members of the immunoglobulin
superfamily (IgSF) and belong to the CTX subfamily, which is characterized by a
membrane-distal V-type Ig domain and a membrane-proximal C2-type Ig-domain
(Fig. 1) . h e JAM family comprises 'sensu stricto' JAMs including JAM-A, JAM-B
and JAM-C and 'sensu lato' JAMs including CAR, ESAM, JAM4 and JAM-L (Ebnet
et al. 2004, Bradi eld et al. 2007a). All JAMs undergo homophilic interactions
that require cis-dimerization followed by trans-homophilic interactions (Fig. 2) .
In addition to their homophilic interactions, several JAMs undergo heterophilic
interaction with either other JAM family members or other cell adhesion molecules
(see below). Most of these interactions serve to regulate the recruitment of
immune cells to sites of inl ammation by mediating the adhesion of leukocytes to
endothelial or epithelial cells (Weber et al. 2007). h e homophilic binding between
JAM-A, -B and -C is weak; the primary role of these homophilic and perhaps
certain heterophilic interactions as well is probably to recruit cytoplasmic proteins
to specii c subcellular locations. In support of this notion, JAMs are expressed in
a large variety of cell types where they localize to specii c membrane domains.
Cell types that express JAM proteins include leukocytes, platelets, epithelial and
endothelial cells, but also germ cells or Schwann cells. In this chapter, we discuss
the pleiotropic functions of JAMs as regulators of inl ammation, as organizers of
specii c membrane domains and as signal transducing molecules. Owing to space
limitations, we focus on the three classical JAM molecules JAM-A, -B and -C.
Fig. 1 Principal organization of JAMs. All JAM family members contain two Ig-like domains, a
membrane distal V-type Ig-like domain and a membrane-proximal C2-type Ig-like domain. h e
extracellular domain contains a potential glycosylation site, the C-terminus bears a type II PDZ
domain-binding motif.