Development and Alteration of Polarity

Abstract

Overall polarization of the plasma membrane of epithelial cells is the sum of the individual polarizations of its components. These individual polarizations in turn, may vary independently in degree (apical/basolateral ratio) and may be expressed at different stages of the cell cycle. They occur in response to cell contacts, nature of the support, and presence of triggering hormones; once established, polarizations may be subject to disruption and resorting. Epithelial cells transcytose receptors, insert membrane mechanisms during a particular period of the cell cycle, remove and relocate misplaced membrane components, and even completely reverse their polarity in the presence of well established TJs. TJs are not responsible for polarization but, ironically, they should be regarded as a result of the polarization process itself (31). The polarization of single cells, such as neurons and muscle cells mentioned at the beginning of this article, may represent extreme cases of cells that polarize but do not produce TJs. However, if an asymmetrically inserted protein is subsequently released from underlying anchoring structures (e.g. the cytoskeleton) to become free (e.g. 50% of Na,K-ATPase in MDCK cells), then the TJ may play a role in confining the free fraction to the apical or to the basolateral region. But even if TJs fail to completely segregate membrane components, mechanisms can restore polarization as in the case of the Na,K-ATPase trapped on the apical side. Lipid polarization seems to depend on the existence of the fence like character of the TJs and to the best of our knowledge lipid polarization is only found in epithelial cells with well established TJs.

Apical localization of PMCA2w/b is enhanced in terminally polarized MDCK cells

“…These experiments suggested an interplay between the alternative splice options at sites A and C in determining the unique localization pattern of the PMCA2 splice variants. However, a limiting factor in these studies was that transient expression of the pump does not allow for longer culture times, which are necessary to ensure full polarization of MDCK epithelial cells [8]. Here, by using stably transfected cells we show that the apical localization of PMCA2w/b is greatly enhanced in filter grown, fully polarized PMCA2w/b-MDCK cell cultures.…”

Sodium/potasium ATPase (Na+, K+-ATPase) and ouabain/related cardiac glycosides: a new paradigm for development of anti- breast cancer drugs?

“…They play a crucial role in the establishment and maintenance of cell polarity of epithelia within tissues [66,67]. TJs constitute the selective pores [68] that transport ions and other substances through the paracellular route [38,69,70]. TJs exist as macromolecular complexes comprised of several types of transmembrane proteins, cytoskeletal proteins, and signaling molecules, including claudins, occludins and Zonula Occludens (ZO) proteins [38,64], many of which are regulated during mammary gland development and pregnancy cycles, and several of which (e.g.…”

Dynamic modeling of the tight junction pore pathway

“…Tight junctions can be regulated rapidly in response to physiological and pathophysiological stimuli . Our prevailing understanding of tight junction function is that there are at least two distinct pathways of tight junction conductance: pore and leak .…”