Proteins that use the secretory pathway for folding and trafficking are over- represented in protein-misfolding diseases....

Proteins that use the secretory pathway for folding and trafficking are over- represented in protein-misfolding diseases. Describe the process of translation and transport through this pathway for a secretory protein?

Expert Solution

Several genetic and sporadic diseases are caused due to protein misfolding. Examples of such diseases are cystic fibrosis ,Alzheimer's, Parkinson's etc

Improperly fold proteins impact the health of the cell regardless of the function of the protein. When proteins fail to fold into their functional state, the resultant misfolded proteins carries shapes that creates problems to the crowded cellular environment

The secretory pathway is a pathway which is composed of the ER, the ERGIC or ER-Golgi intermediate compartment ,the Golgi apparatus, and TGN or the trans-Golgi network . These structures are necessary for protein synthesis, and are important to receptor trafficking .Secretory proteins are those proteins which are synthesised by the cell and then released into outer environment. Mucus, digestive enzymes and hormones are different types of secretory proteins.

The translation process for production of a secretory protein is similar to any other protein. The mRNA is produced which is transported to the cytosol, in the cytosol it interacts with a free cytosolic ribosome.The N-terminal of the peptide, contains a signal sequence of around 6 to 12 amino acids with hydrophobic side chains. A cytosolic protein, SRP (Signal Recognition Particle), recognizes these proteins and stops the translation and aids in the transport of the mRNA-ribosome complex to an SRP receptor found in the endoplasmic reticulum membrane. The dissociation of SRP from the ribosome leads to the restoration of the translation of the secretory protein. The signal sequence is removed and the translation continues while the produced chain moves through the translocon,a complex which moves polypeptide to lumen of endoplasmic reticulum. Proteins meant for use outside the cell, that is the secretory proteins like enzymes and hormones, are kept temporarily inside secretory vesicles before being secreted.

Proteins destined to be secreted move through the secretory pathway in the following order: rough ER → ER-to-Golgi transport vesicles → Golgi cisternae → secretory or transport vesicles → cell surface (exocytosis)

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gladiator answered 1 year ago

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