Polarized Epithelial Cells

Polarized epithelial cells form boundaries between an external or luminal compartment and the extracellular fluid compartment. The biological roles of these cells relate to their location betweeen compartments. First, sheets of polarized epithelial cells form barriers of very selective permiability between compartments. Secondly, they regulate the composition of the two compartments by carrying out specialized vectorial transport between the compartments, manifest as absorption, transcytosis and secretion.

The fundamental characteristic of polarized epithelial cells is organization of its plasma membrane into structurally and functionally distinct domains. More specifically, the polarized epithelial phenotype is characterized by:

One important example of a polarized epithelial cell is the absorptive enterocyte that lines the lumen of the lumen of the small intestine. A critical mission of the small intestine is to absorb glucose - that is, to transport it from the lumen into blood. Glucose cannot pass through the tight junctions, so it must be transported through the epithelial cells. The apical membrane of the cell contains a sodium-dependent glucose transporter that allows the cell to absorb glucose. In the basolateral membrane are sodium-independent glucose transporters that allow the cell to export glucose into extracellular fluid and hence into blood. The polarized phenotype of the cell thus allows a one-way transport of glucose across the cell, as well as a similarly vectorial transport of sodium.

Establishment and maintenance of the polarized phenotype is dependent on development of attachments between cells and between cells and substratum. Attachments between cells are mediated by cell adhesion molecules, specifically E-cadhedin in the case of epithelial cells. Cells attach to the extracellular matrix via a group of cell surface glycoproteins called integrins. Both of these types of attachments are calcium-dependent interactions. The cytoskeleton also plays a critical role in establishment and maintainence of the polarized cell phenotype. Both the cell adhesion molecules and integrins are attached to actin filaments, and once the specialized membrane domains are established, at least some of the proteins are anchored in place through actin filaments.

Development of cell-cell and cell-substratum contacts induces a reorganization of membrane proteins. For example, attachment of a single MDCK cell to an artifical substrate is sufficient to induce polarization of apical membrane marker proteins to the non-attached portion of the plasma membrane in less than one day. In contrast to MDBK cells, mouse L cells are not normally polarized and do not express E-cadhedrin. If however, the E-cadhedrin gene is introduced and expressed in L cells, they rapidly develop extensive cell-cell contacts and assume a polarized phenotype, including redistribution of the Na/K ATPase molecules into discrete domains. A final interesting example is seen in development of the early embryo - in cells of cleavage-stage mouse embryos, the Na/K ATPase is uniformly distributed in the plasma membrane, but as cell junctions form at the morula stage (a process called compaction, which establishes a type of polarized epithelium called trophectoderm), the ATPase gradually becomes localized to the basolateral membrane.

To maintain the polarized phenotype, cells must selectively target membrane proteins and lipids to seperate domains in the plasma membrane. Proteins destined for different membrane domains are codistributed in the ER and cotransported through the Golgi. This suggests that a subsequent sorting step in the trans-Golgi network is involved in segregating proteins and lipids into seperate transport vesicles, which then are somehow targeted to their respective destinations in the plasma membrane.

Alterations in cell membrane polarity are seen in several disease states, and may play an important role in the pathogenesis of many cancers. Normal polarized epithelial cells have a very limited ability to move because they are locked into sheets of epithelium by junctional complexes, cell adhesion molecules and integrins. Carcinomas develop from epithelial cells that loose control of cell growth, malignant carcinomas display invasiveness - the ability to spread widely from the original site of development. It has become clear that alterations in intercellular adhesion and polarization are involved in development of invasiveness in many carcinomas. For example, many of the poorly differentiated and highly invasive carcinomas do not express functional E-cadherin and show a non-polarized phenotype reminiscent of fibroblasts, and there is a good correlation between level of expression of E-cadherin and state of differentitation among tumors of the same type. It is likely that alterations of other elements that maintain the polarized phenotype may contribute to development of the malignant state.

References and Reviews

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Last updated on Sunday, July 28, 1996
Comments: rbowen@lamar.colostate.edu