In: Biology
Your major research project as a graduate student involves analyzing a collection of mutants isolated by your lab all of which have defects in some aspect of the secretory pathway. For each of the mutants below, suggest where in the pathway the mutation might occur. If possible suggest a candidate gene that might be affected in that particular line.
1. Cells grow normally but produce no extracellular matrix
2. Cells grow normally and produce extracellular matrix but have reduced cells do not grow on the matrix
3. Cells do not secrete any protein but they do accumulate hundreds of vesicles
4. Cells do not secrete protein, of accumulate vesicles but have whorls of endoplasmic reticulum
5. Cells do not secrete protein and the ER looks fairly normal but there’s a curious lack of Rough ER
1. A variety of genes involved in control of cell growth and division.The cell cycle is the cells way of replicating itself in an organized step by step fashion.An auxotroph is mutant organism that has an additional nutrional growth requirement,whwn compared with parental organism from which it was derived.
Cells do not produce extracellular matrix because their might be mutation in extracellular matrix producing gene/ECM(extra cellulat matrix) proteins.Their might be alteration in microenvironment focusing on the large macromolecules, that affects extracellular matrix.
Laminins are family of at least 11 glycoproteins form integral part of structural scaffolding of basement membrane. so degradation of that might cause mutations, so cells do not produce extracellular matrix.
2. Remodelling of ECM occurs in many pathological states.changes in the ECM regulated by proteolytic enzymes.so there might be defect in matrix metalloproteinases(MMP) that regulate cell proliferation means cell growth. so deregulation of MMP causes destruction in cell growth.
3. protein secretion is a multistep process that involves vesicle biogenesis.proteins are destined to be secreted in following order, rough ER-ER-golgi trasport vesicles-golgie cisternae-secretory of transport vesicles-exocytosis.
there must be defect in any one of these producing genes. or there must be defect in cell type secretory proteins, which triggers elevation in cytosolic Ca2+ .
4. due to defect in ER proteins cells cannot secrete proteins.unfolded proteins cause an unfolded protein response as a stress response in ER. due to defect in rough ER, smooth ER protein genes, there might be holes in ER.
5. due to lack in rough proteins misfolded proteins do not function properly, and this malfunction even cause human disease. due to this endoplasmic reticulum stress might be developed.defect in proteins, foldase, glycosylating enzymes as well as inappropriate calcium levels affect rough ER.defect in ER lumen, chaperons might cause holes in rough ER.