Cell Junctions & Polarity

What are the three structural domains that define epithelial cell polarity and their respective orientations?

1. Apical domain: Directed toward the exterior surface.
2. Lateral domain: Communicates with adjacent cells.
3. Basal domain: Rests on the basal lamina, anchoring the epithelial cell to the underlying connective tissue (C.T.).

How are cell surface specializations classified according to cell domain?

• Apical specializations: Microvilli, stereocilia, cilia, and flagella.
• Lateral specializations: Intercellular junctions.
• Basal specializations: Basement membrane, hemidesmosomes, and basal & lateral infoldings.

How do microvilli and the glycocalyx appear under light microscopy (L/M), and where are they characteristically located?

Under L/M, they appear as a striated brush border. Characteristic sites include the absorptive cells of the small intestine and the epithelial cells of proximal renal tubules.

What is the internal ultrastructure of a microvillus under electron microscopy (E.M.)?

Each microvillus is a plasma membrane-covered finger-like extension containing a core of cross-linked actin microfilaments. The basal ends of these microfilaments intermingle with the terminal web—a dense apical horizontal filamentous layer that provides rigidity to the cell apex—and the exterior is covered by the glycocalyx (glycoprotein cell coat).

What is the initial pathologic change and underlying cause of Celiac disease (gluten-sensitive enteropathy or sprue)?

One of the first pathologic changes is the loss of microvilli (brush border) on absorptive enterocytes. This is caused by an immune reaction against the wheat protein gluten during digestion, leading to diffuse enteritis, malabsorption, and structural changes that are reversible upon removing gluten from the diet.

What are the structural features, functions, and anatomical sites of stereocilia?

Stereocilia are long, non-motile, irregular microvilli containing arrays of microfilaments and actin-binding proteins anchored to the terminal web, sometimes branching distally. Located in the epididymis and inner ear, they function to increase surface area and facilitate absorption.

What are the four primary types of lateral intercellular junctions?

1. Tight junction (zonula occludens)
2. Adherens junction (zonula adherens)
3. Desmosomes (macula adherens)
4. Gap junction (communicating junction; nexus)

What is the structure, intercellular spacing, and function of a tight junction (zonula occludens)?

Formed by the fusion/sealing of outer cell membrane proteins (claudins and occludins), it completely eliminates the intercellular space ($0\,\text{nm}$) and encircles the cell like a belt. Its functions are to prevent fluid leakage between cells (e.g., in the GIT), create an impermeable barrier (e.g., blood-brain barrier), and provide mechanical strength and stability.

How does a macula occludens differ from a zonula occludens, and where is it found?

Instead of forming a continuous belt-like seal around the entire circumference of the cell, a macula occludens presents as multiple patches of membrane fusion; it is found characteristically in endothelial cells.

What is the structure, intercellular space, and cytoskeletal association of an adherens junction (zonula adherens)?

It encircles the apical part of adjacent cells directly below the tight junction with a $20\,\text{nm}$ intercellular space. Calcium-dependent transmembrane cadherins adhere adjacent cell membranes together, while their cytoplasmic tails attach to actin filaments inside the cells.

What pathological process is clinically associated with the loss of cadherins in adherens junctions?

Loss of cadherins is associated with cancer metastasis.

What is the structure, intercellular distance, and primary function of a desmosome (macula adherens)?

It is a spot-like junction where two opposing cytoplasmic plaques anchor intermediate filaments (keratin) and are joined across a $30\,\text{nm}$ intercellular space by cadherins. It serves as the strongest cell junction type, preventing cell separation under mechanical stress.

What constitutes a junctional complex, and in what apical-to-basal order is it arranged in small intestinal columnar cells?

A junctional complex consists of several junction types that maintain structural and functional integrity between epithelial cells. In small intestinal columnar cells, they are arranged from apical to basal as: zonula occludens, followed by zonula adherens, and then desmosomes (maculae adherentes).

What is the molecular structure of a gap junction (nexus)?

It is formed by the alignment of two opposing connexons from neighboring cell membranes. Each connexon consists of $6$ integral transmembrane proteins called connexins arranged around a central hydrophilic pore.

What are the primary functions of gap junctions, and in which tissues are they essential for contraction?

They enable direct cell-to-cell communication and rapid transfer of electrical and chemical signals. They are essential for coordinated contraction in cardiac muscle and smooth muscle (such as in the gut and uterus).

What is the autoimmune target and clinical manifestation of Pemphigus vulgaris?

It is an autoimmune disorder characterized by autoantibodies produced against the desmosomal proteins of epidermal cells, leading to widespread blistering of the skin and mucous membranes.

How do Clostridium enterotoxin and Helicobacter pylori compromise tight junctions clinically?

• Clostridium enterotoxin binds claudin molecules in intestinal epithelial cells, disrupting tight junctions and causing interstitial fluid loss into the lumen (diarrhea) and ulceration.
• Helicobacter pylori binds extracellular domains of tight-junction proteins in gastric epithelial cells, causing loss of tight junction integrity and contributing to gastric ulcers.

Which medical conditions are linked to mutations in various connexin genes?

Mutations in connexin genes are linked to certain types of deafness and peripheral neuropathy.

What are the three structural layers/components of the basement membrane and their molecular compositions?

1. Basal lamina: Synthesized by epithelial cells; composed of collagen type IV, glycoproteins (laminin), and proteoglycans (heparan sulphate).
2. Reticular lamina: Synthesized by connective tissue cells; composed