Tuesday 3 July 2018

IMPORTANT COMPONENTS OF ECM (EXTRACELLULAR MATRIX)

Elastin -This insoluble fibrous macromolecule provides the resilience (stretch) of the skin, vessels, and ligaments by associating with collagen fibers to limit stretching and preventing tearing. It is highly hydrophobic (proline and glycine), is not glycosylated or "hydroxylized". It has many crosslinks at the lysine residues to stablize the fibers. 

Fibrilin -Is bound in fibers of microfibril sheaths. The sheaths are composed primarily of this protein.
The elastic fiber is made of two alternating segments of hydrophobicity and alpha-helical segments (alanine/ lysine --> crosslinks)

Integrins-This glycoprotein is a cell receptor that interacts with the surrounding ECM, providing anchor for the cell to the matrix of the collagen + links to peptidoglycans.This transmembrane cell receptor is made of alpha and beta subunits that function in cell signaling (depend on extracell divalent cations) and the regulation of cell cycle, shape, and motility through LINKING the ECM with the actin cytoskeleton.  Integrins can mediate indirect interactions with the cytoplasmic cytoskeleton through intermediary proteins including talin and vinculin.


Selectins-Carbohydrate binding proteins that bind to glycoproteins from other cells, important in WBC extravasation, the movement of them from inside the capillaries into the tissues


Multiadhesive proteins -

Dthrombospondin,tenascin,vitronectn,nidogen/enactin,van willebrand factor ,laminin and fobronectin.

A. Laminin- This is a large adhesive glycoprotein that is a major component of BASAL LAMINA. It has binding domains specific for other actors in the BL, including type IV collagen, heparin sulfate (perlecan), enactin (nidogen), and integrins. It consists of 3 poly peptide chains: alpha, beta, gamma

B.Fibronectin -
This example of an adhesive glycoprotein is found in most ECM and plasma. It binds to collagen and proteoglycans. Type III module contains RGD sequence for binding receptors. Importantly, it exists as a protein dimer, consisting of two nearly identical monomers linked by a pair of disulfide bonds.
Although Fibronectin is produced from one gene, it has highly diverse isoforms due to this mechanism in pre-mRNA.

Examples:
- Soluble plasma fibronectin - component of blood plasma made by liver
- Insoluble cellular fibronectin - component of ECM.

Proteoglycans -

A.Aggrecan -This is a major macromolecule of cartilage (made of several GAGs). Due to extensive hydration, it creates a gel-like matrix. These proteoglycans require a core of Hyaluronan and it binds to TGF-beta to inhibit ECM synthesis.

B.Decorin-Is a ubiquitous proteoglycan wide spread in ECM binds to type 1 collagen fibrils and can limit their size and binds TGF-beta and sequesters it interaction with cells.

C.Perlecan -Type of proteoglycan, found in basal lamina, structural and filtering function in basal lamina, the glycosaminoglycan chains attached to perlecan are responsible for preventing proteins escaping from the serum to the urine during glomerular filtration, is one of the proteins that can be defective in specific form of muscular dystrophy.

Notes on collagen -

http://dnaofbioscience.blogspot.com/2016/10/collagen.html



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