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#### LET'S TALK LIFE-SCIENCE CELL BIOLOGY

Suraj Prakash Sharma | Ekta Chotia

298

Adhesion is a primary feature of the cells and many tissues. Many cell surface protein (like CAMs) mediate homophilic (like binds like) adhesion between cells same types of cells and some show heterophilic adhesion between different types of cells. Some proteins like CAMs are usually connected to the cytoskeleton elements.

For example : Sheet of hepatocytes two cells thick makeup much of the liver, sheet of absorptive epithelial cells, forms the  lining of the small intestine.

There are five classes of CAMs (cell adhesion molecules)

2. Selectins
3. Mucins
4. Integrins
5. The immunoglobulin (Ig) super family

Cadherins is a family of hydrophilic cell-cell adherion molecules, or CAMs, which are Ca+2 dependent. These play role during differentiation of tissue. Each cadherins is a type-I, integral membrane glycoprotein. Cadherins is composed of 720-750 amino acids.

The cadherins molecules consists of a single pass extracellular trans membrane spanning segment (at N-terminal) and a cytoplasmic tail which is at c-terminal. The extracellular domain, contains repetitive sequences, necessary for Ca+2 binding and call-cell adhesion. The cytoplasmic tail is associated with the cytoskeleton, via a rambler of intracellular attachment proteins. Cadherins express in both invertebrates and vertebrates.

There are E-cadherin, P-cadherin and N-cadherin, which are most widely expressed, during early differentiation. In adult vertebrates, E-cadherin holds the most epithelial sheets together and mediate homophilic interactions.

9.2.         Integrins :

Integrins are those transmembrane glycoproteins, which act as principal cell matrix adhesion molecules. Integrins are made up of two subunits $\alpha$ and $\beta$, which are non-covalently associated trans membrane glycoprotein, in nature. They are heterodimers. The a subunit binds with divalent cations. The cytoplasmic portion of integrins molecule, binds with adaptor of proteins (venculin, $\alpha$-actinin), which interact with the actin filaments inside the call. The extracellular portion binds to structural proteins (such as collagen) in the extracellular matrix. Most integrins mediate the attachment of cells to the extracellular matrix.

9.3.         Selectins and Immunoglobulin Superfamily

There are two other families also, of transmembrane cell-cell adhesion molecules (CAMs), selections and Ig superfamily. The selectins mediate cell-cell adhesion by heterophilic binding, in which one cell binds to the different kind of adjacent cells. Selectins also depends on extracellular calcium. The Ig family members show homophilic and heterophilic adhesion, both members of this family include vascular and neural cell adherions molecules (VCAM and NCAM), intracellular adhesion molecules (ICAM) and nections and nectin like (NeCl) proteins. The Ig CAMs, leads to signaling within the cell, enables the proteins to function in normal biological processes, as well as pathological events super family.

9.4.         Mucins :

These are a diverse family of density glycoslylated proteins. The main domains are rich in threonine, serine and hydroxyproline, which enables post translation o-glycosylation, Mucins associates with membranes and may serve as receptor like ligands for carbohydrate binding molecules. This properties are resistant to proteolysis and able to hold water and have gel like properties found in mucosal barriers.

9.5.         Cell Junctions

The cell junctions are plentiful in epithelial. They occur at points of cell-cell and cell-matrix contacts. Many cells are linked to one another and to the extracellular matrix by the cell junctions. Which are specialized contact sites.

Functional groups :

1. Occluding junctions
2. Anchoring junctions
3. Communicating junctions

1.            Occluding junctions :

They seal the cells together in a epithelium. In such a way that prevents the small molecules from leaking from one side of the sheet to the other. These junctions are of 2 types :

• Tight junction : These are cell-cell occluding junctions which are mediated by two major transmembrane proteins : Clandins and occludins. These maintain polarity of epithelial cells by functioning as barriers to the diffusion.
• Septate junctions : The septate junctions are the main occluding junctions in invertebrates. They form a continues band around each epithelial cell. Their interacting plasma membranes are joined by proteins, that arrange in parallel rows.

2.            Anchoring junction :

These junctions attach the cells to their neighbours or to the extracellular matrix, mechanically. They play role in holding the cells together by joining the cytoskeletal filaments. Those junctions, include two functionally different forms.

• Adherens junctions : These junctions are formed by transmembrane adhesion proteins, which connect bundles of actin filaments form cell- cell or cell to extra cellular matrix focal adhesions, bind cells to the extracellular matrix are formed by transmembrane adhesion protein of the integrin family and actin filaments.
• Desmosomes : Desmosomes are button like points of intercellular contact, which connect intermediate filaments from cell to cell. These form a structural frameworks of great tensile strength. Desmosomes contain two specialized cadherin proteins, desmoglein and desmocollin. Hemidesmosomes or half desmosomes resemble desmosomes morphologically and in connecting to intermediate filaments, but the intracellular attachment proteins in hemidesmosomes are different from those in desmosome.

(3)          Communicating junctions :

These junctions mediate the passage of chemical or electrical signals from one interacting cell to next cell.

• Gap junctions : Gap junctions are consist of transmembrane proteins called as connexin. Six connexins assemble and form a cylinder which has an open aqueous pore in its centre called as connexon. The connexons hold the interacting plasma membrane at a fixed distance apart. This form a continous aqueous channel, called as gap junction. It connects two cells membranes interiors. Gap junctions allow small ions and small molecules to pass directly from one cell to another.

• Plasmodesmata : The plant cells have only one class of intercellular junctions, called as plasmodesmata. They directly connect the cytoplasm to adjacent cells. At each plasmodesmata, the plasma membrane of one cell is continuous with its neighbour which creat an open channel between the two cytosols. An extension of the smooth endoplasm reticulum in a narrower cylindrical structure, is called as desmotubule. The desmotubules leave a ring of surrounding cytoplasm through which ions and small molecules pass freely between the cells. A new cell wall is assembled during the cytokinesis phase of cell division. The plasmodesmata are created within it, and they form around element of smooth endoplasmic reticulum (ER), which are trapped across the developing cell plate.

Fibronectin Structure

A fibronectin molecule consists of two nearly identical polypeptide chains joined by two disulfide bonds near their carboxyl ends. Each polypeptide chain is folded into a series of domains linked by short, flexible segments. These domains have binding sites for ECM components or for specific receptors on the cell surface. The receptor binding domain contains the tripeptide sequence arginine-glycine-aspartate (RGD), which is recognized by fibronectin receptors. Besides the binding activities noted, fibronectin has binding sites for heparan sulfate, hyaluronate and gangliosides (glycosphingolipids that contain sialic acid groups).

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