Cell junctions
Also known as: tight junction, zonula occludens, adherens junction, zonula adherens, desmosome, macula adherens, hemidesmosome, gap junction, junctional complex, connexin, cadherin, integrin
Specialised protein complexes that seal epithelia (tight junctions), anchor cells to each other and to the basement membrane (adherens junctions, desmosomes, hemidesmosomes) and couple neighbouring cells chemically and electrically (gap junctions).
Overview
In epithelia the apical-most junctions form a junctional complex (terminal bar), from apex to base: tight junction, adherens junction and desmosome.
Occluding junctions — tight junctions (zonula occludens) encircle the apex of each cell as anastomosing strands of claudins and occludin, fusing adjacent membranes. They seal the paracellular space (claudin composition sets how "leaky" an epithelium is to ions and water) and act as a fence separating apical from basolateral membrane proteins, maintaining cell polarity. ZO-1 links them to actin.
Anchoring junctions. Adherens junctions (zonula adherens) form a belt just below the tight junction, where Ca²⁺-dependent E-cadherins bind across the intercellular space and connect, via catenins, to a ring of actin filaments. Desmosomes (maculae adherentes) are spot welds: the desmosomal cadherins desmoglein and desmocollin bind dense plaques (desmoplakin, plakoglobin) anchored to keratin intermediate filaments — abundant where mechanical stress is high (epidermis, myocardium). Hemidesmosomes attach the basal surface to the basement membrane via integrin α6β4 and BP180 (collagen XVII), linked to keratin through plectin and BP230. Focal adhesions link actin to the ECM through other integrins.
Communicating junctions — gap junctions (nexus) are clusters of channels formed by two docked connexons, each a ring of six connexins, bridging a 2–3 nm gap. They pass ions and small molecules (< ≈1 kDa: cAMP, IP₃, glucose) between cells, providing electrical coupling of cardiac and smooth muscle and metabolic coupling in many tissues; they close in response to high Ca²⁺ or low pH, isolating injured cells.
Parts & subdivisions
- Tight junction (zonula occludens)Claudins and occludin; paracellular seal and polarity fence.
- Adherens junction (zonula adherens)E-cadherin–catenin complexes linked to actin.
- Desmosome (macula adherens)Desmoglein/desmocollin + plaque proteins linked to keratin filaments.
- HemidesmosomeIntegrin α6β4 + BP180 linking keratin to the basal lamina (laminin-332).
- Gap junctionConnexon channels (6 connexins each) for intercellular communication.
Function
- Seal epithelia and maintain apical–basal polarity.
- Distribute mechanical stress across tissues.
- Anchor epithelium to the basement membrane.
- Permit electrical and metabolic coupling (synchronised contraction of the heart).
- Contact inhibition and signalling (cadherin–β-catenin).
Clinical significance
Pemphigus vulgaris vs bullous pemphigoid
Pemphigus: IgG against desmoglein 3 (± 1) → loss of keratinocyte adhesion (acantholysis), flaccid intra-epidermal blisters and oral erosions, Nikolsky positive. Bullous pemphigoid: IgG against hemidesmosomal BP180/BP230 → tense subepidermal blisters in the elderly, oral mucosa usually spared, Nikolsky negative.
Loss of E-cadherin in cancer
Down-regulation of E-cadherin allows epithelial–mesenchymal transition, invasion and metastasis. Germline CDH1 mutations cause hereditary diffuse gastric cancer (signet-ring cells) and lobular breast carcinoma.
Connexin disorders
GJB2 (connexin 26) mutations are the most common cause of inherited non-syndromic sensorineural deafness; connexin 32 mutations cause X-linked Charcot–Marie–Tooth neuropathy. Arrhythmogenic cardiomyopathy involves desmosomal protein mutations (plakophilin-2).
Mnemonics
Order of the junctional complex (apical → basal)
"Tight, Adhere, Desmo" — zonula occludens, zonula adherens, macula adherens; then hemidesmosomes at the base. Gap junctions are scattered along the lateral membrane.
Test yourself
Autoantibodies against desmoglein 3 produce blisters by disrupting which junction?
- Tight junction
- Gap junction
- Desmosome
- Hemidesmosome
Answer: Desmosome
Desmogleins are desmosomal cadherins. Anti-desmoglein antibodies cause pemphigus vulgaris (intra-epidermal acantholysis). Antibodies against hemidesmosomes (BP180/BP230) cause bullous pemphigoid (subepidermal blisters).
Which junction allows direct passage of ions and small molecules (< ≈1 kDa) between neighbouring cells, coupling cardiac myocytes electrically?
- Zonula occludens
- Zonula adherens
- Gap junction
- Hemidesmosome
Answer: Gap junction
Gap junctions are made of connexons (hexamers of connexins) that align across a 2–3 nm gap. In the heart they lie in the intercalated discs (connexin 43).
Compiled from standard anatomy and physiology references — see the Cells & Tissues sources. For education only; not medical advice.