Epithelial polarity

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Epithelial polarity is one example of the

epithelial sheets
that line cavities and surfaces throughout the animal body. Each plasma membrane domain has a distinct protein composition, giving them distinct properties and allowing directional transport of molecules across the epithelial sheet. How epithelial cells generate and maintain polarity remains unclear, but certain molecules have been found to play a key role.

A variety of molecules are located at the

Cdc42, atypical protein kinase C (aPKC), Par6, Par3/Bazooka/ASIP.[1] Crumbs, "Stardust" and protein at tight junctions (PATJ). These molecules appear to form two distinct complexes: an aPKC-Par3-Par6 "aPKC" (or "Par") complex that also interacts with Cdc42; and a Crumbs-Stardust-PATJ "Crumbs" complex. Of these two complexes, the aPKC complex is the most important for epithelial polarity, being required even when the Crumbs complex is not. Crumbs is the only transmembrane protein in this list and the Crumbs complex serves as an apical cue to keep the aPKC complex apical during complex cellular shape changes.[citation needed
]

Basolateral membranes

In the context of

interstitial fluids.[2]

Basal and lateral membranes share common determinants, the proteins LLGL1, DLG1, and SCRIB. These three proteins all localize to the basolateral domain and are essential for basolateral identity and for epithelial polarity.

Mechanisms of polarity

How epithelial cells polarize is still not fully understood. Some key principles have been proposed to maintain polarity, but the mechanisms behind these principles remain to be discovered.

The first principle is positive feedback. In computer models, a molecule that can be either membrane-associated or cytoplasmic can polarize when its association with the membrane is subject to positive feedback: that membrane localization occurs most strongly where the molecule is already most highly concentrated. In similar models, researchers have shown that epithelial cells can self-assemble into a rich set of robust biological shapes.[3] In the yeast saccharomyces cerevisiae, there is genetic evidence that Cdc42 is subject to positive feedback of this kind and can spontaneously polarize, even in the absence of an external cue. In the fruit fly Drosophila melanogaster, Cdc42 is recruited by the aPKC complex and then promotes the apical localization of the aPKC complex in a probable positive feedback loop. Thus, in the absence of Cdc42 or the aPKC complex, apical determinants cannot be maintained at the apical membrane and consequently, apical identity and polarity is lost.

The second principle is segregation of polarity determinants. The sharp distinction between apical and baso-lateral domains is maintained by an active mechanism that prevents mixing. The nature of this mechanism is not known, but it clearly depends on the polarity determinants. In the absence of the aPKC complex, the baso-lateral determinants spread into the former apical domain. Conversely, in the absence of any of Lgl, Dlg or Scrib, the apical determinants spread into the former baso-lateral domain. Thus, the two determinants behave as if they exert mutual repulsion upon one another.

The third principle is directed

vesicle
delivery. A related mechanism is likely to operate for the baso-lateral membranes.

The fourth principle is lipid modification. A component of the lipid bilayer,

phosphatidyl inositol
phosphate (PIP) can be phosphorylated to form PIP2 and PIP3. In some epithelial cells, PIP2 is apically localised while PIP3 is basolaterally localised. In at least one cultured cell line, the MDCK cell, this system is required for epithelial polarity. The relationship between this system and the polarity determinants in animal tissues remains unclear.

Basal versus lateral

Since basal and lateral membranes share the same determinants, another mechanism must make the difference between the two domains. Cell shape and contacts provide the likely mechanism. Lateral membranes are the site of contact between epithelial cells, whereas basal membranes connect epithelial cells to the basement membrane, an extracellular matrix layer that lies along the basal surface of the epithelium. Certain molecules, such as Integrins, localise specifically to the basal membrane and form connections with the extracellular matrix.

Epithelial cell shape

Epithelial cells come in a variety of

shapes that relate to their function in development or physiology. How epithelial cells adopt particular shapes is poorly understood, but it must involve spatial control of the actin cytoskeleton
, which is central to cell shape in all plant cells.

Apocrine cells, showing apical snouts towards the lumen.

Apical snouts, also called apical blebs, are small protrusions of cytoplasm towards the lumen. They are found normally in apocrine cells, and can also appear in apocrine metaplasia and columnar cell changes in the breast.[4]

Epithelial cadherin

All epithelial cells express the transmembrane

adherens junctions
that connect the actin cytoskeletons of neighbouring cells. Adherens junctions are the primary force-bearing junctions between epithelial cells and are fundamentally important for maintaining epithelial cell shape and for dynamic changes in shape during tissue development. How E-cadherin localizes to the boundary between apical and lateral membranes is not known, but polarized membranes are essential for maintaining E-cadherin at adherens junctions.

See also

References

Bruce Alberts; Alexander Johnson; Julian Lewis; Martin Raff; Keith Roberts; Peter Walter, eds. (2002). Molecular Biology of the Cell (4th ed.). Garland Science.

ISBN 978-0-8153-3218-3
.

  1. PMID 9763423
    .
  2. PMID 16403838
    .
  3. PMID 30477635
    .
  4. doi:10.1186/s42047-018-0027-2.{{cite journal}}: CS1 maint: multiple names: authors list (link
    )
  5. PMID 7790378
    .
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