Term
Human Diseases Resulting fromInability of Proteins to Exit the ER
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Definition
•Cystic fibrosis - CFTR protein is retained and degraded in the ER. Chloride regulation is lost in epithelial cells.
•Tay-Sachs disease - Beta-hexosaminidase does not reach lysosomes. Glyco-lipids accumulate in lysosomes leading to endocrine and neurological defects.
•Hereditary emphysema - a1-antitrypsin (inhibitor of elastase) is retained in ER. Elastin is degraded in lung.
•Diabetes mellitus - Class 2 mutations in the insulin receptor impairs transport to the cell surface.
•Familial hypercholesterolemia - Mutations in the LDL receptor prevent this protein from reaching the cell surface. This results in defects in LDL transport and leads to increases in serum levels of cholesterol.
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Term
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Definition
•Any information found in the primary amino acid sequence and/or tertiary structure to direct the protein to appropriate intracellular compartment.
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•This information can be contiguous or dis-contiguous.
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•ER signal sequence peptides are a good example.
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•Protein sorting signals are recognized by transmembrane “receptors” that couple binding of the intralumenal protein to proteins that direct of the formation of a budding vesicle.
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•Mannose 6-phosphate is a signal that directs transport of hydrolases to lysosomes.
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Term
Lysosomal Storage Disease
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Definition
•Lysosomal storage diseases are due to the absence of one or more lysosomal enzyme. Undigested glycolipids and extracellular components accumulate in lysosomes as large inclusions.
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•I-cell disease is a severe form of lysosomal storage disease in which multiple enzymes are missing from lysosomes. Patients are missing the GlcNAc phosphotransferase required to generate M6P. Other diseases in this class include: Tay-Sachs disease and Gaucher’s disease. These primarily affect the nervous system.
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•Many cells in patients with I-cell disease contain normal levels of appropriately targeted hydrolases. This and other experimental evidence has demonstrated that there is also a M6P -independent targeting pathway in many cells.
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Term
Sorting of Secretory Granule Proteins
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Definition
-Certain specialized cells store secretory proteins in vesicles and secrete them only when they receive the appropriate stimulus.
-Insulin secretion from b-pancreatic cells, trypsinogen secretion from acinar cells, and ACTH secretion from pituitary cells are all examples of this.
-Many of these proteins are synthesized as precursor polypeptides that are processed in maturing granules.
-The formation of a mature secretory granule involves a number of steps including protein sorting, formation of immature granules, pro-protein processing and vesicle fusion.
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Term
Proteins destined for secretion move through the secretory pathway in the following order |
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Definition
-RER to the Golgi via vesicles, through the Golgi, and to the cell surface or targeted to lysosomes or secretory granules. |
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Term
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Definition
-Mediate Transport from the ER to the Golgi
-also contain certain proteins that bind specific soluble and integral membrane proteins for transport from the ER to the Golgi. |
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