Lecture 23 – Cell Junctions

Q: In neutrophil trapping, which molecules on endothelial cells bind to carbohydrates on neutrophils?

Selectins.

Q: What do platelet activating factor (PAF) and IL-8 from endothelial cells bind to on neutrophils?

G-protein coupled receptors (GPCRs).

Q: During transendothelial migration, which neutrophil molecules bind to ICAM/VCAM on endothelial cells?

Integrins.

Q: What is the basement membrane (basal lamina)?

A specialized extracellular matrix (ECM) — not a lipid bilayer membrane like the plasma membrane.

Q: What are the five types of cell junctions found in epithelial cells?

Tight junctions, adherens junctions, gap junctions, desmosomes, and hemidesmosomes.

Q: What three junctions make up the "junctional complex"?

Tight junctions (zonula occludens), adherens junctions, and desmosomes (macula adherens).

Q: What defines the apical vs. basolateral domains of an epithelial cell?

The tight junction divides the membrane — the apical domain is above the TJ, and the lateral membrane (contiguous with the basal membrane) forms the basolateral domain below.

Q: What are the two functions of tight junctions?

Gate function (controls paracellular passage of ions, proteins, and water between cells) and fence function (blocks diffusion of integral membrane proteins between apical and basolateral domains, maintaining cell polarity).

Q: What happens when claudin-1 (a tight junction protein) is mutated?

Death due to dehydration, tight junctions can no longer retain water.

Q: What cytoskeletal element do tight junctions connect to?

Actin filaments (and microtubules), but they do not contribute to tissue strength.

Q: Do tight junctions contribute to tissue strength?

No — they control solute passage and maintain cell polarity but do not provide mechanical strength.

Q: What is the function of adherens junctions?

They connect the external environment to the actin cytoskeleton, provide a signal transduction pathway from the exterior to the cytoplasm and nucleus, and form a belt (zonula adherens) encircling the cell near its apical surface.

Q: Which cytoskeletal element do adherens junctions bind?

Actin filaments.

Q: What type of cadherins are found in adherens junctions?

E-cadherins (also shared with desmosomes as desmosomal cadherins).

Q: What is the primary function of desmosomes?

Adhesion — they anchor the intermediate filament (keratin) cytoskeleton between two cells, providing mechanical strength to a sheet of cells.

Q: Which cytoskeletal element do desmosomes bind?

Keratin intermediate filaments.

Q: What is the electron-dense plaque in a desmosome?

A cytoplasmic plaque on the inner surface of the plasma membrane formed by cadherin interactions with multiple intracellular proteins, into which keratin intermediate filaments insert.

Q: What is the function of gap junctions?

Cell-to-cell communication — they form intercellular channels that transmit small soluble signaling molecules directly between the cytoplasms of adjacent cells.

Q: What proteins make up gap junctions, and how are they organized?

Connexin proteins — 6 connexins from one cell form a connexon; two connexons (one from each cell) align to form a gap junction channel with a central pore.

Q: What is the size limit for molecules passing through gap junctions?

~1000 Daltons. Lucifer yellow dye (smaller than 1000 Da) can pass through.

Q: Where are hemidesmosomes located and what is their function?

At the basal surface of epithelial cells; they anchor cells to the underlying basement membrane, providing stationary strength.

Q: Which cytoskeletal element and adhesion protein are associated with hemidesmosomes?

Keratin intermediate filaments, linked to the ECM by integrins. Key proteins include BP180 and laminin-5.

Q: What are focal adhesions?

Dynamic, discrete sites of cell attachment to the substratum that play a key role in cell locomotion. They link the actin cytoskeleton to the ECM via integrins.

Q: What signaling kinases are activated at focal adhesions, and why are they important?

Focal adhesion kinase (FAK) and SRC kinase are activated when integrins bind extracellular proteins. They send survival signals to the cell — without this activation, the cell dies.

Q: How do cancer cells exploit the focal adhesion survival pathway?

Circumvent the requirement for integrin-mediated FAK/SRC activation, allowing them to survive without normal ECM attachment.

Q: Compare hemidesmosomes and focal adhesions in terms of cytoskeleton, adhesion protein, and function.

Hemidesmosomes: keratin intermediate filaments, integrins, stationary strength. Focal adhesions: actin cytoskeleton, integrins, dynamic/motility. Both use integrins to contact the substratum.