Fig. 4. Molecular basis of homotypic, interneuronal and heterotypic junctions. (A) AJs and TJs. At AJs, E-cadherin serves as an essential CAM. The cytoplasmic region binds ß-catenin, which in turn binds -catenin. -Catenin is associated with the circumferential F-actin bundles directly and indirectly through vinculin and -actinin. Nectin also functions as a CAM at AJs, but is more highly concentrated at AJs than E-cadherin. The cytoplasmic region binds afadin that is directly associated with the F-actin bundles. Afadin and -catenin are associated with each other presumably through an unidentified molecule `X'. At TJs, claudin and JAM function as CAMs. Occludin is another transmembrane protein at TJs. The cytoplasmic regions of claudin, JAM and occludin bind ZO-1, ZO-2 and ZO-3. ZO-1 and ZO-2 are directly associated with F-actin and form a dimer with ZO-3. Afadin and ZO-1 may be associated with each other through an unidentified molecule `Y'. F-Actin and peripheral membrane proteins shown in the right-side cell are omitted in the left-side cell. (B) Synapses. At the synapses between mossy fiber terminals and pyramidal cell dendrites in the CA3 area of hippocampus, both synaptic junctions and puncta adherentia junctions are highly developed. At the puncta adherentia junctions, nectin-1 and nectin-3 localize asymmetrically at the presynaptic and postsynaptic sides, respectively. Afadin, N-cadherin and catenins localize symmetrically at the both sides. Synaptic junctions are associated with presynaptic active zones where synaptic vesicles, Ca²⁺ channels and many other components, such as bassoon, localize and with PSDs where neurotransmitter receptors localize. F-Actin shown in the postsynaptic side is omitted in the presynaptic side. (C) Sertoli-cell—spermatid junctions. Nectin-2 in Sertoli cells and nectin-3 at spermatids form a hetero-trans-dimer at Sertoli-cell—spermatid junctions. The F-actin bundles surround the spermatid heads like parallel rings (3D view). The nectin-based adhesive membrane microdomains show one-to-one linkage with each F-actin bundle. ES contains not only F-actin bundles but also a flattened cistern that is connected to microtubules.