Biomedical Engineering Reference
In-Depth Information
(62,63). Each of the desmocollin genes also produces splice variants (64). It
is not clear that the individual desmogleins and desmocollins intereact
through homophilic adhesion in the same way as classical cadherins.
Similar to focal adhesions, desmosomes include a complex of cytoplas-
mic proteins that enable connections to the cytoskeleton. Plakoglobin is
related to beta-catenin, which is present in adherens junctions with
E-cadherin (61,65). Plakoglobin is present in other types of cell-cell junc-
tions with or without the classic cadherins (66). Plakophilin is related to
plakoglobin and may bind directly to intermediate filaments. Desmoplakin
also functions to anchor intermediate filaments to desmosomes. Other
proteins present in the plaque on the cytoplasmic side of a desmosome
include the bullous pemphigoid antigen (BPAG1), plectin, and IFAP300.
Similar to focal adhesions, desmosomes may transduce signals (67) and
are important in development of the lung (68,69). Perhaps more important
to injury and repair, the function of desmosomes is modulated by several
stimuli. Garrod et al. (67) have reviewed data that suggest that stimuli such
as wounding can revert stable desmosomes from calcium independence to
calcium dependence. The function of desmosomes is likely regulated by
reversible protein phosphorylation. In this regard, it interests that activation
of PKC is known to modulate desmosome function. As will be discussed
later in this chapter, PKC activation is associated with increased mobility
of epithelial cells. Modulation or disassembly of desmosomes may be neces-
sary for cell migration.
Gap junctions are present on the lateral surfaces of airway epithelial
cells and allow communication between the cells (70). Gap junctions have
specific structural proteins called connexins. Some of the connexins are
relatively specific for the lung (71-73). Gap junctions allow second messen-
gers such as cAMP and Ca
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to diffuse from cell to cell which facilitates
coordination of cilia beating and secretion amongst cells. Proinflammatory
cytokines modulate gap junction-mediated communication (74).
C. Basement Membrane
The basement membrane is a special class of extracellular matrix that under-
lies many cell types including epithelial, endothelial, muscle, and nerve cells
(75). The subepithelial basement membrane forms a barrier that separates
epithelial cells from other cells and provides physical support. The basement
membrane influences epithelial cell differentiation, polarization, and under-
standing its structure is key to understanding epithelial function. Some
components of the basement membrane such as laminin 5 are involved
in development and morphogenesis (69).
The basement membrane under the airway epithelium has not been
subjected to detailed chemical analysis. Much of our understanding of base-
ment membranes comes from studies of basement membranes where there is
