Microvilli, which are small projections of the apical plasma membrane, are typically 1 to 3 µm in length. They are not able to move and their main function is to increase surface area. Cells that need to transport large quantities of ions, water, and molecules, such as the epithelial cells in the small intestine and the cells of the renal proximal tubule, commonly have microvilli. The core of microvilli is composed of actin filaments and various accessory proteins. These actin filaments are connected to the cytoskeleton of the cell through the terminal web, which is a network of actin fibers found at the tight junctions of epithelial cells.

Epithelial cell tight junctions, also known as zonula occludens, consist of several integral membrane proteins including occludins, claudins, and members of the immunoglobulin superfamily such as the junctional adhesion molecule (JAM). Occludins and claudins are transmembrane proteins that span the membrane of one cell and link to the extracellular portion of the same molecule in the adjacent cell. Cytoplasmic linker proteins such as tight junction protein (ZO-1, ZO-2, and ZO-3) then connect the transmembrane proteins to the cytoskeleton of the cell.

Among these junctional proteins, claudins play an important role in determining the permeability characteristics of the tight junction, particularly in relation to cations and anions. So far, 27 mammalian claudin genes have been identified, with 26 found in the human genome (the gene for claudin 13 is absent in humans). Certain claudins act as barrier proteins that limit the movement of ions through the tight junction, while others form a "pore" that facilitates ion movement through the junction. Thus, the permeability characteristics of the tight junction in an epithelium are determined by the specific claudins expressed by the cell.

For example, the proximal tubule of the kidney is considered a "leaky" epithelium, allowing water and solutes like Na+ to pass through the tight junction. Claudin 4 and claudin 10 are expressed in the tight junction of proximal tubule cells. In contrast, the collecting duct of the kidney is considered a "tight" epithelium, with restricted movement of ions through the tight junction. Collecting duct cells express claudins 3, 4, 7, 8, 10, and 18.

The function of claudins can be regulated at various levels, including gene expression, post-translational modification, interaction with cytoplasmic scaffolding proteins, and interaction with other claudins within the same membrane (cis-interaction), as well as with claudins of adjacent cells (trans-interaction). The mineralocorticoid hormone aldosterone stimulates Na+ reabsorption in the distal segments of the renal nephron. In addition to its effect on Na+ transporters within the cell, aldosterone also upregulates the expression of claudin 8 in the tight junction. The increased expression of claudin 8 reduces the ability of Na+ to permeate the tight junction, thereby decreasing the backward leak of Na+ from the interstitium into the tubule lumen and allowing more efficient Na+ reabsorption by the epithelium.
2.9A ). Microvilli are small (typically 1 to 3 µm in length), nonmotile projections of the apical plasma membrane that serve to increase surface area. They are commonly located on cells that must transport large quantities of ions, water, and molecules (e.g., epithelial cells lining the small intestine and cells of the renal proximal tubule). The core of the microvilli is composed of actin filaments and a number of accessory proteins. This actin core is connected to the cytoskeleton of the cell via the terminal web (a network of actin fibers at
Epithelialcelltightjunctions(alsocalledzonula occludens)arecomposedofseveralintegralmembraneproteins,includingoccludins, claudins, andseveralmembersoftheimmunoglobulinsuperfamily(e.g.,thejunctional adhesion molecule [JAM]).Occludinsandclaudinsaretransmembraneproteinsthatspanthemembraneofonecellandlinktotheextracellularportionofthesamemoleculeintheadjacentcell.Cytoplasmiclinkerproteins(e.g.,tightjunctionprotein[ZO-1,ZO-2,andZO-3])thenlinkthemembranespanningproteinstothecytoskeletonofthecell.
Ofthesejunctionalproteins,claudinsappeartobeimportantindeterminingthepermeabilitycharacteristicsofthetightjunction,especiallywithregardtocationsandanions.Todate,27mammalianclaudingeneshavebeenidentified,and26arefoundinthehumangenome(thegeneforclaudin13isnotfoundinhumans).Certainclaudinsserveasbarrierproteinsthatrestrictthemovementofionsthroughthetightjunction,whereasothersforma“pore”thatfacilitatesthemovementofionsthroughthejunction.Thusthepermeabilitycharacteristicsofthetightjunctionofanepitheliumaredeterminedbythecomplementofclaudinsexpressedbythecell.Forexample,theproximaltubuleofthekidneyistermeda“leaky”epithelium,inwhichwaterandsolutes(e.g.,Na+)movethroughthejunction.Claudin4andclaudin10areexpressedinthetightjunctionofproximaltubulecells.Incontrast,thecollectingductofthekidneyisconsidereda“tight”epithelium,withrestrictedmovementofionsthroughthetightjunction.Collectingductcellsexpressclaudins3,4,7,8,10,and18.
Thefunctionofclaudinscanberegulatedatseverallevels,includinggeneexpression,posttranslationalmodification,interactionswithcytoplasmicscaffoldingproteins,andinteractionswithotherclaudinsinthesamemembrane(cis-interaction),aswellaswithclaudinsofadjacentcells(trans-interaction).ThemineralocorticoidhormonealdosteronestimulatesNa+ reabsorptionbydistalsegmentsoftherenalnephron(see ).Inadditiontothehormone’seffectonNa+ transportersinthecell,aldosteronealsoupregulatesexpressionofclaudin8inthetightjunction.Theincreasedexpressionofclaudin8reducestheabilityofNa+ topermeatethetightjunction,whichthenreducesthebackwardsleakofNa+ fromtheinterstitiumintothetubulelumen,therebyallowingmoreefficientNa+ reabsorptionbytheepithelium.