Biomedical Engineering Reference
In-Depth Information
disturb or retard TJ formation in cultured epithelial cells. h e function of JAM-A
in TJ formation thus most likely resides in targeting the Par-aPKC complex to sites
of cell-cell contacts where it is required to establish specii c membrane domains.
h is role of JAM-A might be of particular importance during cell-cell contact
formation. In the absence of cell-cell adhesion, for example, during migration,
cells form thin protrusions to scan the extracellular environment. h e protrusions
are dynamic in the absence of cell-cell adhesion, and they are stabilized upon
cell-cell contact formation (Adams
et al.
1998). Signals mediated by the adhesion
molecules regulate the further maturation of the cell-cell contacts
.
Interestingly,
JAM-A is among the proteins that are present at the earliest sites of cell-cell
adhesion during contact formation, the so-called primordial, spot-like junctions
or puncta. h e Par-aPKC complex is recruited shortly at er the puncta are formed.
h us, a primary role of JAM-A might be to recruit the Par-aPKC complex and
thereby regulate the correct localization of this complex, which regulates the
further cell contact formation that eventually leads to fully matured lateral cell-
cell contacts with TJs localized at the apex and separated from AJs. In accordance
with this view, ectopic expression of a JAM-A mutant that cannot bind Par-3 leads
to defects in the formation of functional TJs and in the development of apico-basal
polarity (Rehder
et al.
2006).
Interestingly, a similar function albeit in a dif erent cell type seems to be true
for JAM-C as well as revealed in JAM-C knockout mice. h e inactivation of the
JAM-C gene in mice leads to male sterility (Gliki
et al.
2004), and the reason for
the sterility turned out to be a blockade in the development of spermatids. During
normal spermatogenesis, spermatids undergo intimate contacts with Sertoli
cells, and this interaction in part is mediated by JAM-C and JAM-B expressed
by spermatids and Sertoli cells, respectively. Cell polarity proteins such as Par-6,
aPKC and Cdc42 are localized in close proximity of the site of spermatid-Sertoli
cell interaction. h is polarized localization is lost in JAM-C knockout spermatids,
resulting in a blockade of spermatid polarization and ultimately in sterility (Gliki
et al.
2004). h us, JAM-C expressed by spermatids provides another example of
the functional role of JAMs: through homophilic and heterophilic interactions,
JAMs are localized to specii c subcellular sites, and through their cytoplasmic
domains, they recruit their binding partners to the specii c localizations where
these are required to regulate developmental processes.
A recent report describes the localization of JAM-C at autotypic junctions
of Schwann cells in myelinated nerves (Scheiermann
et al.
2007). Schwann cells
wrap around the axons to allow for saltatory conduction. At specii c sites such
as the paranodal loops and Schmidt-Lanterman incisures, the Schwann cells
form tight interactions between membrane patches of the same cell, and these
tight interactions are necessary for ei cient electrical insulation. In the absence
of JAM-C, the integrity of the myelin sheath is altered and nerve conduction is
defective. It is not clear yet whether this defects results from a lack of adhesive
