Cell junctions (INTERCELLULAR JUNCTIONS)

1.Adhesion- (Adherens junction attach to actins ) zonula adherens (in epithelial tissue and intercatalated disc)

Cell adhesion relies upon specialized transmembrane cellular adhesion molecules (CAMs) that usually extend from the intracellular space to the extracellular space where they may bind to other cell membranes or to the extracellular matrix. Within the intracellular domain, adhesion proteins adhere directly to or  coupled to, the cell's cytoskeleton.
 Cadherin (calcium dependent adhesion) molecules are normally coupled by special linking proteins – catenins – to the cytoskeleton.

Desmosomes-Allows for stretching .Cytoplasmic plaques of 2 cells bind with the aid of intermediate filaments of keratin.
(In stomach ,bladder and heart )

2.Intermediate filaments are about 10 nm diameter . Provide tensile strength for the cell and connect adjacent cells through desmosomes (macula adherens).
1. Integrins with heterophilic attachments to different (hetero) ligands in the extracellular matrix.
2. Selectins with heterophilic attachments to carbohydrate ligands
3. Ig superfamily proteins with selectins with heterophilic attachments to: a) Integrin ligands 
 b) Ig superfamily proteins of a different (hetero) type, andhomophilic attachments to the Ig superfamily proteins of the same (homo) type.
4. Cadherins with homophilic attachments to cadherins of the same type, or by way of catenins .

Cell adhesion is important in:
1. embryogenesis (morphogenesis)
2. migration of single cells such as leukocytes within multicellular organisms
3. maintaining contact between neuronal elements
4. virulence of virions and bacteria
Some signaling molecules act as adhesion receptors, and cluster in focal adhesions upon ligand binding. (Rho protein). A variety of integrins, which are transmembrane heterodimeric adhesion receptors are known to support adhesion-dependent growth factor-activation of MAP kinase. Focal adhesions are rich in tyrosine phosphorylated proteins, coupling cell adhesion to signal transduction pathways in the cell. 
Various adhesion receptors, such as integrin, are closely linked to protein kinases and phosphatases. 
Grb2 links focal adhesion kinase (FAK) to the Ras pathway when Grb2 is phosphorylated after binding to FAK. The 85 kDa subunit of the PI 3-kinase is also phosphorylated after binding to FAK. Thus, FAK is a key component in the assembly of focal contact structures that influence cytoskeletal organization and signal transduction.
Engagement of ICAM-1, a member of the immunoglobulin supergene family (Ig), has been documented to activate specific kinases through phosphorylation, resulting in activation of transcription factors, increased cytokine production, increased cell membrane protein expression, production of reactive oxygen species, and cell proliferation.


3 .Tight Junctions-(zonula occludens )
Epithelia are sheets of cells that provide the interface between masses of cells and a cavity or space (a lumen).

• The portion of the cell exposed to the lumen is called its apical surface.
• The rest of the cell (i.e., its sides and base) make up the basolateral surface.

Tight junctions seal adjacent epithelial cells in a narrow band just beneath their apical surface. They consist of a network of claudins which are stabilised by spectrin. They interact with spectrin by adapter proteins ZO1 AND ZO2.
Tight junctions perform two vital functions:

• They limit the passage of molecules and ions through the space between cells. So most materials must actually enter the cells (by diffusion or active transport) in order to pass through the tissue. This pathway provides tighter control over what substances are allowed through.
• They block the movement of integral membrane proteins (red and green ovals) between the apical and basolateral surfaces of the cell. Thus the special functions of each surface, for example
  • receptor-mediated endocytosis at the apical surface
  • exocytosis at the basolateral surface
  can be preserved.

EXAMPLES---Intestine ,kidneys and epithelium of skin 

The epithelial cells of the human lung expressa growth stimulant, called heregulin, on their apical surface andits receptors on the basolateral surface. (These receptors also respond to epidermal growth factor (EGF), and mutant versions have been implicated in cancer. 

4.Gap Junctions-  (communicating junction) directly proportional to stability .

Gap junctions are intercellular channels some 1.5–2 nm in diameter. These permit the free passage between the cells of ions and small molecules (1000 daltons).

They are cylinders constructed from 6 copies of transmembrane proteins called connexins.

Because ions can flow through them, gap junctions permit changes in membrane potential to pass from cell to cell.
Examples:

• The action potential in heart (cardiac) muscle flows from cell to cell through the heart providing the rhythmic contraction of the heartbeat.
•  Electrical synapses in the brain, gap junctions permit the arrival of an action potential at the synaptic terminals to be transmitted across to the post-synaptic cell without neurotransmitters and receptors .
• As the time of birth approaches, gap junctions between the smooth muscle cells of the uterus enable coordinated, powerful contractions to begin.
• Present in skin epithelium ,endocrine glands,smooth muscle,osteocytes and glial cells.
• (BETWEEN CELLS AND MATRIX ---------------                   HEMIDESMOSOME) plectin adapter protein is present .Cell matrix adhesion attach cells to basal lamina.

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