Chapter 19 Omega

Two broad types of cell linkages

cell–cell junctions and cell–ECM (extracellular matrix) attachments — cell–cell junctions mediate tissue cohesion while cell–ECM linkages anchor cells to the matrix.

What bears most mechanical stress in tissues

The cytoskeleton (actin filaments and intermediate filaments) and their attachments (adherens junctions/desmosomes and focal adhesions/hemidesmosomes) bear most mechanical stress.

Types of cell junctions (Fig. 19-2)

Tight junctions (seal and partition membrane domains), adherens junctions (cadherin–actin belts), desmosomes (cadherin family linking to intermediate filaments), gap junctions (connexin channels for small molecule exchange), and hemidesmosomes/focal adhesions (cell–ECM anchors).

Cadherins and superfamily

Cadherins are Ca²⁺-dependent transmembrane adhesion proteins

Homophilic binding

Homophilic binding = cadherins on one cell bind the same cadherin type on an adjacent cell (like-with-like), promoting selective cell–cell adhesion.

How cadherins bind and break

Cadherin extracellular repeats bind each other in a Ca²⁺-dependent conformation

Strength of cadherin attachments

Individual cadherin bonds are relatively weak, but many bonds in parallel plus cytoskeletal linkage make the overall junction mechanically strong.

Specificity of cadherins

Cadherin expression is cell-type specific — different cells express different cadherin combinations, driving selective adhesion and tissue sorting.

Cadherin changes in nervous development

Neural development shows dynamic cadherin expression: progenitors and migrating neurons switch cadherin types over time, guiding aggregation, layer formation, and synaptic matching.

Sorting-out process (Fig. 19-9)

Cells expressing different cadherins segregate by preferential homophilic binding until like cells cluster (differential adhesion/sorting).

Catenins: location & function

β-catenin (and plakoglobin) bind cadherin cytodomains

Assembly of an adherens junction

Cadherin extracellular domains mediate cell–cell contact, their cytoplasmic tails bind β-catenin (or plakoglobin) which recruits α-catenin to connect to actin, forming a belt-like junction.

Why adherens junctions are mechanotransducers

Tension across cadherin–catenin complexes causes conformational changes (e.g., α-catenin unfolding) that expose binding sites and trigger downstream signaling — mechanical force is converted to biochemical signals.

Role of vinculin

Vinculin is recruited to force-exposed sites (e.g., unfolded α-catenin or talin), binds actin and stabilizes force-bearing junctions, amplifying mechanotransduction.

Adhesion belt: function & components

The adhesion belt is a circumferential adherens junction composed of cadherins, catenins, actin filaments and associated proteins

Folding an epithelial sheet into a tube

Apical constriction driven by actin–myosin contraction in adhesion belts narrows cell apices, bending the sheet and forming a tube — coordinated changes in cell shape drive morphogenesis.

Desmosomes & hemidesmosomes

Desmosomes are spot welds between cells made of desmoglein/desmocollin (cadherin family) linked via plakoglobin/plakophilin and desmoplakin to intermediate filaments

Polarity of epithelial cells

Epithelial cells are polarized with distinct apical, lateral, and basal domains defined by junctional complexes (tight junctions apically, adherens/desmosomes laterally, basal adhesions to ECM).

Tight junction molecular structure

Tight junctions are strands of claudin family proteins (form paracellular pores with selectivity) and occludin, connected intracellularly to scaffold proteins (ZO family) and actin

Claudins vs occludins

Claudins are the primary pore-forming proteins that determine paracellular ion selectivity

Scaffold proteins & PDZ domain at tight junctions

Scaffold proteins (ZO-1, ZO-2, ZO-3) contain PDZ domains that bind the C-terminal motifs of claudins/occludin, organizing junctional complexes and linking them to the actin cytoskeleton and signaling molecules.

Gap junctions: structure & subunits

Gap junction channels are formed by two docked hemichannels (connexons), each a hexamer of connexin subunits (animals).

What passes through gap junctions

Small ions, metabolites, and second messengers (generally molecules < ~1 kDa) pass through gap junctions, enabling metabolic and electrical coupling.

Action potentials via gap junctions

Yes — in electrically coupled tissues (e.g., heart, some neurons), ionic currents can pass through gap junctions to support rapid electrical transmission (electrical synapses).

Regulation of gap junction gating

Gap junctions open or close in response to voltage differences, intracellular Ca²⁺, pH, phosphorylation state, and other factors.

Plasmodesmata structure & function

Plasmodesmata are plant cell membrane-lined channels containing a central desmotubule (ER continuum) that allow direct cytoplasmic continuity and transport of small molecules, proteins, and some RNAs between plant cells.

Selectins: structure & function

Selectins are Ca²⁺-dependent lectin adhesion molecules (L-, E-, P-selectin) that bind carbohydrate ligands on leukocytes to mediate transient rolling on endothelium during inflammation.

Selectins and integrins in leukocyte migration

Selectins mediate initial weak rolling

Ig superfamily (ICAMs, NCAMs)

Ig-superfamily CAMs include ICAMs (ligands for integrins, mediate leukocyte adhesion) and NCAMs (neural cell adhesion molecules that use homophilic and heterophilic interactions in neural development and synapse formation).

ECM overview: variation & secretion

The extracellular matrix ranges from loose hydrated gels (connective tissues) to dense fibrous matrices (tendon)

Three classes of ECM macromolecules

1) Fibrous proteins (collagens, elastin), 2) glycosaminoglycans/proteoglycans, and 3) adhesive glycoproteins (fibronectin, laminin).

GAGs: structure, charge, hydration

Glycosaminoglycans are long, unbranched, repeating disaccharides heavily sulfated or acidic, carry a strong negative charge, are highly hydrophilic and attract water — ideal for resisting compression.

Hyaluronan

Hyaluronan (hyaluronic acid) is a very large, non-sulfated GAG synthesized at the plasma membrane, provides space-filling, lubrication, and a scaffold for proteoglycan aggregate formation.

Proteoglycans: structure & function

Proteoglycans are core proteins with covalently attached GAG chains

Aggrecan and decorin

Aggrecan is a large cartilage proteoglycan that aggregates with hyaluronan to resist compression

Collagen: structure & variation

Collagen is a triple-helix of three α-chains (Gly-X-Y repeats) that assemble into fibrils and networks

Where collagen mRNAs are translated

Collagen α-chain mRNAs are translated on rough ER ribosomes where nascent chains undergo proline/lysine hydroxylation and glycosylation.

Proline/lysine modifications & disease

Selected prolines and lysines are hydroxylated (require vitamin C) and some lysines are oxidatively crosslinked

Procollagen processing to ECM

Procollagen folds into a triple helix in the ER, is secreted, propeptide ends are cleaved extracellularly, and fibrils are crosslinked (lysyl oxidase) to form stable collagen fibers in the ECM.

Variation in collagen organization

Collagen is organized into loose networks, aligned fibrils, or dense parallel bundles depending on tissue function

Elastin: structure & secretion

Elastin is secreted as soluble tropoelastin which is crosslinked extracellularly (lysyl oxidase) into an elastic network that provides reversible extensibility

Fibronectin structure & RGD

Fibronectin is a dimeric adhesive glycoprotein containing modular domains including the RGD peptide motif that is recognized by integrins

Fibronectin assembly

Fibronectin fibrillogenesis occurs at the cell surface where integrin binding plus cell-generated tension unfolds fibronectin to expose assembly sites

Basal lamina: basic structure & three organization modes

Basal lamina is a thin, sheet-like ECM under epithelia composed mainly of laminin, type IV collagen, nidogen, and perlecan

Cells that synthesize basal lamina & components

Basal lamina is synthesized by the cells it underlies (epithelial cells, muscle cells, Schwann cells)

Lamina and type IV collagen functions

Laminin forms a cell-binding polymer that organizes the basal lamina

Functions of the basal lamina

Basal lamina functions include structural support, filtration (kidney glomerulus), scaffold for cell migration, cell polarity cues, and compartmentalization.

ECM degradation importance

Rapid ECM degradation enables tissue remodeling, cell migration, morphogenesis, and wound repair.

Metalloproteases and serine proteases

Matrix metalloproteases (MMPs) are Zn²⁺-dependent enzymes that cleave ECM proteins

Integrins: structure & associated components

Integrins are α/β heterodimeric transmembrane receptors that bind ECM ligands extracellularly and connect to intracellular adaptors (talin, kindlin, paxillin, vinculin) and the actin cytoskeleton at focal adhesions.

Integrin activation/inactivation

Integrins switch from low- to high-affinity states by inside-out signals (talin/kindlin binding to β tail) and by extracellular ligand binding (outside-in)

Why integrins cluster

Clustering increases overall binding strength (avidity), forms focal adhesions for signaling and force transmission, and concentrates signaling molecules for coordinated responses.

Anchorage dependence & cancer

Anchorage dependence means many cells require ECM attachment for survival and proliferation

Talin as a tension sensor

Talin links integrin β tails to actin

Plant cell wall components & turgor pressure

Primary plant cell walls contain cellulose microfibrils embedded in a matrix of hemicelluloses and pectins

Cellulose structure

Cellulose is long β-1,4-linked glucose chains that hydrogen-bond to form strong microfibrils.

Primary wall arrangement of polymers

In the primary wall cellulose microfibrils are embedded in a network of cross-linking glycans (hemicelluloses) and held in a hydrated pectin matrix, producing a load-bearing but extensible composite.

Orientation of cellulose microfibrils & cell elongation

The orientation of cellulose microfibrils determines the direction of cell expansion — microfibrils oriented circumferentially restrict lateral expansion and bias elongation along the axis