Cell Adhesion and Motility

What is the main function of cell adhesion in tissues?

Anchoring cells within tissues to maintain tissue/organ integrity and generate physical barriers between compartments.

What are Cell Adhesion Molecules (CAMs)?

Transmembrane proteins that mediate cell-cell or cell-ECM adhesion; main families are cadherins, Ig superfamily, selectins, and integrins.

What ion do cadherins require for binding?

Calcium (Ca2+).

What structural repeats characterize the Ig family of CAMs?

Immunoglobulin (Ig) domains.

What domain do selectins use to bind carbohydrates?

A lectin-like domain.

What are the three selectin types listed and their repeat counts?

P-selectin (9 repeats), E-selectin (6 repeats), L-selectin (2 repeats).

What is homophilic binding?

Binding between two identical adhesion molecules on opposing cells (e.g., cadherin-cadherin, Ig-Ig).

What is heterophilic binding?

Binding between two different types of molecules (e.g., selectin binding a carbohydrate ligand).

What is the structure of an integrin?

A heterodimer of one alpha and one beta chain.

How many alpha and beta integrin chains exist, and how many receptor combinations?

18 alpha chains and 8 beta chains, forming 24 or more distinct alpha-beta receptors.

What determines integrin ligand specificity?

Integrin receptors are tissue- and ligand-specific.

What cellular processes do integrins regulate?

Cell motility, proliferation, differentiation, and apoptosis.

What type of signaling do integrins engage in?

Both outside-in and inside-out signaling.

What ligands does the beta1 integrin subunit typically bind?

Collagens, laminin, and fibronectin (depending on the alpha partner).

What ligands does beta2 integrin (alphaL, alphaM, alphaX) bind?

ICAM-1, ICAM-2, C3b, fibrinogen, and Factor X.

What does fibronectin link integrins to?

The extracellular matrix (collagen fibrils) on one side and the actin cytoskeleton (via adaptor proteins) on the other.

What are the five main types of intercellular/cell-matrix junctions?

Tight junction, adherens junction, desmosome, gap junction, and hemidesmosome.

What does a tight junction do?

Seals neighboring epithelial cells to prevent leakage of molecules between them and maintains cell polarity.

What proteins form tight junction sealing strands?

Claudins and occludins, bound homophilically.

What does an adherens junction join?

An actin bundle in one cell to a similar actin bundle in a neighboring cell.

What mediates adherens junction adhesion?

Cadherins, via calcium-dependent homophilic binding.

What cytoskeletal linker proteins connect cadherins to actin at adherens junctions?

Alpha-actinin and vinculin.

What does a desmosome join between cells?

Intermediate filaments in one cell to those in a neighboring cell.

What cadherins mediate desmosome adhesion?

Desmocollin and desmoglein.

What proteins link intermediate filaments to the desmosome plaque?

Desmoplakin, plakoglobin, and plakophilin.

What is the functional benefit of many desmosomes together?

They impart great tensile strength to epithelial sheets.

What does a hemidesmosome anchor?

Intermediate filaments in a cell to the underlying basal lamina.

What integrin and plaque proteins are found in hemidesmosomes?

Integrin (PB180) and plectin/PB230 linking to keratin filaments.

What happens to a cell sheet without intermediate filaments when stretched?

The cells rupture, unlike sheets with intermediate filaments which remain intact.

What do gap junctions allow to pass between cells?

Ions and small molecules under about 1500 daltons, such as intracellular messengers.

What structural unit forms a gap junction channel?

A connexon, a hexagonal array of six connexin subunits; two connexons align to form one channel.

How can gap junction channels be gated?

By calcium, pH, or second messengers.

What is a "zonula" (zona) junction?

A belt-type junction encircling the cell, formed by tight and adherens junctions.

What is a "macula" junction?

A spot-type junction, including adherens-only spots, desmosomes, and hemidesmosomes.

What is the adhesion belt and what does it enable in epithelial sheets?

A continuous band of adherens junctions with associated actin filaments that allows coordinated tightening, driving invagination of epithelial sheets (e.g., neural tube formation).

What is an adhesion plaque in a migrating cell?

A cluster of integrins linked via talin, vinculin, paxillin, and FAK to actin stress fibers, anchoring the cell to fibronectin in the substratum.

What kinase is recruited to adhesion plaques and associates with Src?

Focal adhesion kinase (FAK).

What small GTPases regulate actin stress fiber formation at adhesion plaques?

Rho GTPases.

What is a lamellipodium?

A sheet-like actin-rich protrusion at the leading edge of a migrating cell, formed by branched actin networks.

What is a filopodium?

A thin, spike-like protrusion containing bundled, parallel actin filaments.

What protein nucleates branched actin filaments in lamellipodia?

The Arp2/3 complex.

What protein attaches actin filaments to the plasma membrane in filopodia/contractile bundles?

Formins.

What proteins bundle actin filaments within filopodia?

Fascin and fimbrin.

Describe the four steps of process protrusion in cell migration.

(1) Lamellipodium extends at leading edge, (2) new adhesions form and trailing edge forms, (3) tail retracts as new adhesion points form, (4) cell body moves forward.

What balances the position of the lamellipodium tip in a stationary cell?

Actin polymerization is balanced by myosin-driven retrograde flow of F-actin.

What allows a lamellipodium to extend forward instead of just flowing backward?

Stable attachment to the substrate via integrins resists the retrograde actin flow, converting polymerization into forward extension.

What is chemotaxis?

Directional cell movement along a gradient of increasing chemoattractant concentration.

What is an example of chemotaxis in the immune system?

A neutrophil (white blood cell) migrating toward and chasing bacteria.

What is leukocyte rolling mediated by?

Selectins binding to mucins/carbohydrate ligands on the endothelium.

What activates integrins on a rolling leukocyte?

Chemokines and inflammatory triggers (e.g., infection, allergen, tumor) signaling through the leukocyte.

What mediates firm adherence of an activated leukocyte to endothelium?

Activated integrins binding intercellular adhesion molecules (ICAMs) on the endothelium.

What is extravasation?

The process by which an adherent leukocyte migrates out of the blood vessel through the endothelium into the tissue.