L3: Cell Biology II Flashcards
Types of proteins found in plasma membrane
- Peripheral
- Integral proteins (including transmembrane proteins)
What is occurring at cellular level in Alzheimer’s disease?
- Abnormal cleavage of Beta-amyloid precursor protein, beta-app into alphabeta peptides, which aggregate and are resistant to proteolysis. This precursor protein is important in neuronal migration in development, synaptic formation and repair, cell signaling, long-term potentiation, memory and cell adhesion.
What is occurring at the cellular level in Creutzfeldt-Jakob disease?
- CJD occurs when PrP (normal prior protein), which is a cell-surface glycosylated GIP anchored protein (in lipid rafts) on neurons is converted into an abnormal variant.
- The variant forms cross-linked filaments and is resistant to proteolysis
- In addition, variant accelerates conversion of other proteins to its form
- Normal proteins may be neuroprotective against ischemia, control circadian rhythms and serve to organize myelin sheath
- Symptoms: ataxia, dementia and paralysis
Functions of proteins in plasmalemma
- Receptors
- Transport
- Enzymatic control of chemical rxns
- Linker proteins for structural support
- Cellular ID tags (antigens)
- Intercellular junctional complexes
Name specific chemical transport proteins. Function?
- Na/K pump: regulates intracellular volume, electrochemical gradient
- Ca/Na transporter
- Glucose/sodium co-transport pump utilizing Na/K pump
- Multidrug resistant transporters: primary transporter proteins that are ATases. MDR-1 (kidney, liver, intestine and BBB) pumps cytotoxic agents out of cell. MDR-2 transports conjugated (direct) bilirubin. MDR-3 (liver) functions as flippase of PC, flipping to the outer layer of hepatocytes so that it may be excreted into bile
Function of digoxin
- Digoxin partially inhibits Na/K pump leading to decreased activity of Ca/Na transporter, leading to an increase in sarcoplasmic Ca ion concentration, which improved cardiac pump performance
Difference between pump and carrier?
- Pump requires direct expenditure of energy
- Carrier doesn’t require direct expenditure of energy
What can overexpression of MDR-1 proteins cause? Clinical relevance?
- Cancer cells to become resistant to cytotoxic drugs
- This is targeted intervention with RNA interference and pharmacologic inhibitors
What protein in the plasma membrane is defective in Dubin-Johnson syndrome?
- Mutations in ATP binding region of MDR-2, therefore impaired transcription and mislocalization of the MDR-2 protein
Discuss what is occurring at the cellular level in nephrogenic diabetes insipidus
- Aquaporin-2 is expressed in renal collecting tubule cells and reabsorbs water
- Vasopressin (ADH) receptor causes translocation of aquaporins to plasmal membrane and increase reabsorption of water across apical surface.
- This disorder results when both aquaporin-2 is inactivated by mutations and therefore doesn’t respond to vasopressin signaling
- As a result, glucose is concentrated in blood
Discuss what is occurring at the cellular level in Cystic Fibrosis?
- CFTR is a chloride channel, also regulates Na and HCO3-
- In CF, CFTR is not put up on the cell surface as a result of defect in glycosylation
- Chloride and Na not brought into the cell, leads to salty sweat
- Airway: normal mucous has sodium extracted from it, chloride gets added and water is taken out. In CFTR, sodium and water are extracted from it making it viscous and dehydrated.
- Also leads to viscous secretions in intestines, pancreas and bile duct. Ductus deferens becomes obstructed too.
Examples of proteins that perform enzymatic reactions at cell’s apical surface
- Digestive enzymes on epithelial cells of small intestine
- Lactase in GI system, cleaves lactose into galactose and glucose
What is occurring at the cellular level in Duchenne’s and Becker’s muscular dystrophy?
- Dystroglycans (extracellular) and dystrophin (intracellular) are structural proteins that anchor cells plasma membrane to underlying cytoskeleton.
- Dystrophins are not present in DMD
Function of CHOs in plasma membrane
- CHOs are attached to lipids and proteins forming glycolipids and glycoproteins respectively
- Have negative charges which repel other negatively charged substances – keep RBCs aapart
- React with regulatory molecules
- Play a role in cell-cell and cell-matrix recognition and adhesion
- Protection
Describe what is occurring at cellular level with cholera toxin
- Ganglioside GM1 is a glycolipid that serves as a cell receptor for cholera toxin
- Toxin enters cell by binding GM1
- Causes increased synthesis of cAMP
- Causes a substantial efflux of Na ions and water into intestine (for example) – net result = diarrhea
