  Though membrane trafficking of cell junction proteins has been studied
extensively for more than two decades, the accumulated knowledge remains
fragmentary. The goal of this review is to synthesize published studies on the
membrane trafficking of the five major junction transmembrane proteins:
claudins, occludin, and junction adhesion molecules (JAMs) in tight junctions;
cadherins and nectins in adherens junctions; to identify underlying common
mechanisms; to highlight their functional consequences on barrier function; and
to identify knowledge gaps. Clathrin-mediated endocytosis appears to be the
main, but not exclusive, mode of internalization. Caveolin-mediated endocytosis
and macropinocytosis are employed less frequently. PDZ-domain binding is the
predominant mode of interaction between junction protein cytoplasmic tails and
scaffold proteins. It is shared by claudins, the largest family of junction
integral proteins, by junction adhesion molecules A, B, and C, and by the three
nectins. All eight proteins are destined to either recycling via Rab4/Rab11
GTPases or to degradation. The sorting mechanisms that underlie the specificity
of their endocytic pathways and determine their fates are not fully known. New
data is presented to introduce an emerging role of junction-associated scaffold
proteins in claudin membrane trafficking.
