This will be our last podcast for epithelium and it will be fairly brief
now we have in our previous two podcasts, we've looked at epithelial cell polarity
and we've considered concepts of the apical domain of epithelium and just to
remind you that the apical domain is always directed to the exterior surface
or the luminal surface of an enclosed cavity or tube. We've looked at
junctional complexes on the lateral domain of epithelium and we've
emphasized that these junctional complexes are important to hold adjacent
cells together and they play a role of course in cell to cell communication. In
this last podcast, we want to talk a little more about the basal domain of
epithelium and remind you that all epithelium rests on a basement membrane
and this functions to anchor the epithelial cells to the underlying
connective tissue. With regard to the basal domain, we can talk about cell to
extracellular matrix junctions that anchor epithelial cells to their
extracellular matrix and we've already mentioned focal adhesions and hemidesmosomes.
Now oftentimes, you'll see basil infoldings of the plasma membrane
to increase surface area and this will facilitate morphological interactions
between adjacent cells and extracellular matrix proteins. Sometimes you'll also
see membrane infoldings to increase surface area depending on
the physiologic function of the epithelium. So here, for example, in this
electron micrograph, we show membrane infoldings in renal tubules and we can see
interdigitated mitochondria in these membrane infoldings and this is very
characteristic of cells that are involved in active transport, which of
course occurs in some of the renal tubules,
the mitochondria provide the ATP energy for active transport.
Now the basement membrane is a specialized structure. It's located next
to the basal domain of epithelial cells and it involves the underlying
connective tissue stroma. Now the basal lamina is synthesized by epithelial
cells and the reticular lamina is synthesized by connective tissue cells.
Taken together the basement membrane consists of a basal lamina and a
reticular lamina. We're going to talk about two components of the basal lamina,
a lamina lucida and a lamina densa, the basal lamina as we said is synthesized
by epithelial cells. We're going to suggest to you that the lamina lucida
may well be a preparation artifact although it is talked about in histology
textbooks as a distinct structure. The major protein in the basal lamina is
collagen type 4 there are other colleges involved in the basal lamina in addition
to other collegens, there are laminins, there's proteins like entactins,
proteoglycans, and fibronectin, but for the purposes of this course the major
protein associated with basal lamina is collagen type 4. the basal lamina as we
said is synthesized by epithelial cells. The major protein in the reticular
lamina is primarily collagen type 3 and as we said the reticular lamina is
synthesized by cells of connective tissue. Now what are the functions of the
basal lamina, first the basal lamina supports epithelium and it separates
epithelium from the underlying connective tissue, the basal lamina can
induce differentiation of epithelium, it will also contain ligands for cell
surface receptors in the epithelial cells. These receptors when they bind
their ligand can initiate signaling cascades which as you might imagine from
your studies in biochemistry can establish a second
messager functions and can turn on transcription factors to affect gene
expression. Basal lamina can influence metabolic activities of the epithelium
the basal lamina especially and the glomerulus of the kidney performs a very
important function as a selective filtration barrier. The basal lamina also
enhances wound healing and epithelial repair. It serves as a scaffold
essentially for repair and the basal lamina of epithelium can enhance nerve
and muscle regeneration in injured organs. This is an simple-minded cartoon
and it makes the point that the basal lamina is a product of both epithelial
cells and connective tissue cells so here we show some epithelial cells in
diagrammatic fashion and here some connective tissue cells. The basement
membrane consists of the basal lamina which is synthesized by the epithelial
cells and the reticular lamina which is synthesized by connective tissue cells
and by the way the most common connective tissue cells would be
fibroblasts and smooth muscle cells. As we've suggested, the lamina lucida may be
a preparation artifact. It appears in tissues when the tissues affixed with
chemical fixation but if one does more modern low-temperature, high pressure
freezing techniques you don't see a lamina lucida. Components of the basal
lamina, as we said, collagen type 4 is a major component. It is unique to the
basal lamina. It's found in the lamina densa. Collagen type 4 provides the
structural framework for the basal lamina. It is heavily glycosylated.
Collagen 4 forms relatively small fibrils that did not form the large
fibers that you studied in biochemistry. Collagen 4 is highly flexible. The C
terminal ends can dimerize as suggested in this cartoon and the end terminal
ends might form networks with each other. Heparan sulfate is another component of
basal lamina. Heparan sulfate basically are sulfated glycosaminoglycans. These
sulfated glycosaminoglycans provide a fairly high negative charge to the basal
lamina. There are other proteins like entactins that form almost like a glue
type structure and then finally Perlecans which are larger components that
are combinations of heparan sulfate and some of the various entactins or
protein glues. Another fairly significant component of the basal lamina is laminin
and laminin is a large cross shaped protein. It is on the order of a million
daltons and laminins bind various components of the basal lamina to each
other and to epithelial cells. Laminin is actually a protein consisting of three
different protein chains, an alpha chain, a beta chain, and a gamma chain and
that's shown here in this kind of cross configuration and then it shows there
are regions in the laminin molecule that bind to cells. There are regions in the
laminin molecules that bind to collagen and there are regions in the laminin
molecule that bind to heparan sulfate. So the diagram on the bottom suggests that
this laminin, not only is it binding to cells, but it's binding to a variety of
some of the extracellular matrix proteins. Here is a more complicated
cartoon of this with the diagram on the top showing the epithelial cells and so
the basal lamina highlighted here would be shown here in the diagram, so if you
imagined flipping these epithelial cells upside down here is the lipid bilayer of
the epithelial cells. Here are some of the
integrin proteins that we talked about in our last podcast and then a variety
of these extracellular matrix proteins and you can get a sense of the fairly
substantial mesh work that is forming in part of this basal lamina and note that
integrin's transmembrane proteins in the epithelial cells have receptors that
bind onto some of these proteins in the extracellular matrix. Now this interval
of a network of proteins in the basal lamina determines its function. So you'll
have structural attachment of epithelium to the connective tissue.
There'll be compartmentalization such that epithelia and also nerve and muscle
are separated from connective tissue. As we said, the basal lamina serves as a
filtration barrier in the renal corpuscle. It allows movement to
substances to and from epithelium and that filtration is in part regulated by
the basal lamina. The basal lamina can serve as a tissue scaffold guide for
cell migration during morphogenesis and regeneration and it can also serve as an
important barrier to invasion of cells during tumor metastasis. The basal lamina
plays a role in cell signaling and regulation during morphogenesis. It plays
the same role in fetal development, in wound healing, in proliferation. It's
involved in motility of cells and because it has receptors in the membrane
that will recognize proteins in the basal lamina, it can play a role in gene
expression and also in apoptosis or cell death. Something we're going to talk
about in more detail as we go along in the course, cells can be polarized and so
epithelial cells can be polarized both structurally and functionally and as a
result, epithelial cells may have a certain amount of asymmetry to them. So
we can talk about asymmetry of cell surfaces. We've already talked in previous
podcasts about apical lateral and basal domains in epithelial cells. The apical
domain may have cilia on it. It may have microvilli on it or stereocilia, there
could be a glycocalyx, which is oftentimes PAS positive, and this can be
associated with the apical domain of epithelial cells. The lateral domain of
epithelial cells will contain junctions that bind cell to cell. These junctions
can hold the cells together and these junctions can also play a role in cell
to cell communication. The basal surface of epithelial cells will have junctions
that bind the epithelial cells to the extracellular matrix and the membrane in
the basal areas may be thrown into folds to increase membrane surface area. There
can be distinct plasma membrane domains in epithelial cells so the apical domain
may have various ion permeabilities. We looked for example at the sodium glucose
symporter, the basal lateral domain may have glucose carriers, especially in
epithelial cells. They'll oftentimes be sodium potassium ATPase molecules at the
basolateral domain of epithelial cells, and this will be important in
maintaining the ionic differences across cell membranes. And epithelial
cells can be polarized with respect to their organelles. They can be polarized
in the biosynthetic or exocytosis pathway so they'll be an array of ER
Golgi and secretory vesicles that will move towards the plasma membrane.
Epithelial cells may also be polarized in the endocytic pathway, so you could
absorb lipids. You can have diffusion that can be resynthesis, formation of
chylomicrons and this is all things you may have studied in biochemistry and
that will touch upon as we go through the course.
This cartoon gives an example of polarization of epithelial cells with
respect to plasma membrane domains, so you may be bringing material into the
epithelial cells from a lumen and these materials may transport across the
epithelial cells and maybe exocytosed at the basal side of the epithelial cells.
As we suggest there are some junctional complexes in epithelial cells. We've
talked about the sodium glucose symporter. We'll talk about endocytic and exocytic
vessel formation. We've talked about glucose carriers and we've
mentioned, for example, the sodium potassium ATPase and there are sodium
potassium antiporters that can be found in the basal domain of epithelial
cells. We will talk about cell polarization with respect to organelles
and we will talk about cell polarization with respect to vesicle flow in cells.