Epithelial Transport


Epithelia form linings throughout the body. In the small intestine, for instance, the simple columnar epithelium forms a barrier that separates the lumen from the internal environment of the body (note that the internal environment in which body cells exist is the extracellular fluid or ECF).  The epithelium forms a barrier because cells are linked by tight junctions, which prevent many substances from diffusing between adjacent cells.  For a substance to cross the epithelium, it must be transported across the cell's plasma membranes by membrane transporters.

Not only do tight junctions limit the flow of substances between cells, they also define compartments in the plasma membrane.  The apical plasma membrane faces the lumen.  In the drawing, the apical plasma membrane is drawn as a wavy line, because intestinal epithelial cells have a high degree of apical plasma membrane folding to increase the surface area available for membrane transport (these apical plasma membrane folds are known as microvilli).  The basolateral plasma membrane faces the ECF.  Epithelial cells are able to transport substances in one direction across the epithelium because different sets of transporters are localized in either the apical or basolateral membranes.


Absorption

Absorption is the means whereby nutrients such as glucose are taken into the body to nourish cells. Glucose is transported across the apical plasma membrane of the intestine by the sodium-glucose cotransporter (purple). Because transport of Na+ and glucose is coupled, we need to add the free energy inherent in Na+ transport to the free energy inherent in glucose transport to get the overall free energy for the process. Just after a meal, there will be abundant glucose in the lumen of the intestine, favoring absorption. Towards the end of the absorptive phase of a meal, however, the cotransporter is still able to move glucose into the cell (uphill against its concentration gradient) because of the strong Na+ concentration gradient. The Na+ gradient is established by the Na+/K+-ATPase (red), which is located on the basolateral membrane. The activity of the cotransporter increases the glucose concentration inside the cells, allowing glucose to be transported into the ECF via the glucose transporter (blue).  Facilitated diffusion of glucose into the ECF is a passive process, since glucose flows down its concentration gradient.


Secretion

About 1500 ml of fluid per day is moved from the extracellular fluid into the lumen of the small intestine in order to provide lubrication that can protect the epithelium and help with intestinal motility. The mechanism for fluid secretion is that solutes are moved across the epithelium, which then draw water into the lumen by osmosis. The rate-limiting and regulated step in intestinal secretion is the movement of Cl- ions across the apical plasma membrane.

The important proteins involved in secretion are diagrammed in the figure. First, Cl- is transported into the epithelial cell by a cotransporter expressed on the basolateral membrane. As with the previous example, the Na+ gradient, established by the Na+/K+-ATPase, provides the energy to power transport of ions into the cell (this cotransporter moves 2 Cl-, one K+, and one Na+ ion with each round of transport).  Cl- flows down its concentration gradient into the lumen via the Cl- channel CFTR (green) located on the apical plasma membrane. (Not shown is that Na+ also flows into the lumen, by a passive mechanism).

Regulation of Secretion

The CFTR protein is a member of the ATP-binding cassette (ABC) protein family. CFTR is an atypical ABC protein; like other members of the ABC protein family, it binds ATP, but in this case ATP binding is used to open an ion channel. Importantly, the CFTR protein also has a regulatory domain that is phosphorylated by protein kinase A (PKA), also known as cAMP-dependent kinase. Intestinal secretion is turned on when a regulatory molecule binds a G-protein coupled receptor, causing the alpha subunit of the G-protein to activate the enzyme adenylyl cyclase. Adenylyl cyclase produces the second messenger cAMP, which activates PKA to phosphorylate CFTR.  The channel opens when both ATP is bound and the regulatory domain is phosphorylated.



Quick Quiz


Fill in Answer Correct False Correct Answer
1. What structure prevents substances from moving between adjacent cells in the intestinal epithelium?
2. What protein generates the gradient that powers the transport of glucose across the apical plasma membrane of an epithelial cell?
3. Where is the above protein located, in the apical or basolateral membrane?
4. When glucose moves across the basolateral membrane and into the ECF, is this a passive (not requiring energy) or an active (requiring energy) process?
5. The regulated step in the secretion of fluid into the lumen of the intestine is the movement of Cl- across the_________(apical or basolateral?) plasma membrane.
6. Name the enzyme that is responsible for phosphorylation of CFTR.


(Spelling must be correct)