Figure 12.

The apical polarization of Na⁺, K⁺-ATPase in polarized ARPE-19 cells is regulated by the β₂ subunit. An illustration of polarized ARPE-19 cells cultured for 4 weeks on permeable inserts in the presence of ITS is depicted; the cells are relatively tall, express RPE markers and form adjacent tight junctions (TJs). Our model proposes that extracellular signals trigger transduction pathways that activate re-morphogenesis. In non-polarized ARPE-19 cells, a basolateral targeting mechanism carries α₁β₁ and α₁β₃ dimers to the lateral membrane (gray vesicles). The β₁-β₁ (and perhaps β₃-β₃) trans-interaction between neighboring cells stabilizes and retains these dimers at the lateral membrane domain for housekeeping. Upon the triggering of re-morphogenesis, a concurrent apical targeting mechanism is activated by the association of the α₂ and β₂ subunits. α₂β₂ is delivered to the apical domain (magenta vesicles). In cultures, this complex probably does not stabilize at the apical plasma membrane but accumulates in a sub-apical compartment. In situ, the pump is inserted in the apical membrane domain, where it is probably stabilized by heterotypic trans interaction(s) of the β₂ subunit with adhesion proteins on the outer segments of the photoreceptor (β₂-X).