Biomedical Engineering Reference
In-Depth Information
JAMs REGULATE THE ORGANIZATION OF CELL-CELL
CONTACTS IN VARIOUS CELL TYPES AND TISSUES
h rough their cytoplasmic tails, JAMs directly interact with various cytoplasmic
proteins. All these proteins contain one or several PDZ domains, a domain
consisting of 80 to 90 AA that is used to mediate protein-protein interactions. PDZ
domain-containing proteins, in particular those containing multiple PDZ domains,
are frequently used to assemble multiprotein complexes at the membrane. JAM-A,
-B and -C all contain a conserved motif that mediates the interaction with PDZ
domains, and the interactions with the hitherto known direct binding partners,
i.e., AF-6/afadin, ZO-1, Par-3 and MUPP1, are mediated through this motif and a
PDZ domain of the binding partner
(Fig. 5)
(Ebnet
et al.
2004).
h e i rst clear evidence for a role of JAMs in the organization of cell-cell
contacts came with the identii cation of the cell polarity protein Par-3 as direct
binding partner for JAM-A (Ebnet
et al.
2001). Par-3 forms a complex with Par-6
and atypical PKC (aPKC) that localizes to the tight junction (TJ). h e TJs represent
a specii c structure at the most apical region of the lateral cell-cell contact that is
implicated in the regulation of paracellular permeability but also in the separation
of the apical from the basolateral membrane domain (Tsukita
et al.
2001). A
critical role for the Par-aPKC complex for the formation of functional TJs is
suggested by the observations that overexpression of dominant-negative mutants
or siRNA-mediated downregulation of individual components of the complex
Fig. 5
Cytoplasmic proteins directly associating with JAM-A. JAM-A interacts with various
cytoplasmic proteins through specii c PDZ domain interactions. h e PDZ domain involved in
JAM-A interaction is shown in light gray. h e interaction with ZO-1 and PAR-3 is conserved in
JAM-B and JAM-C, interactions with AF-6/afadin and CASK have not been tested yet.
