EXAM1_L6_Cytoskeleton_vesicular_Transport Flashcards
What structure and proteins of Intermediate filaments?
Dimers- self assemble- end to end/side to side
Keratin (EC’s)
Vimentin (fibroblasts)
Neurofilaments (neurons)
Intermediate filament protein in Epithelial cells called.
keratin
Vimentin
intermediate filament protein found in fibroblasts
What is intermediate filament protein found in fibroblast cells?
Vimentin
What causes ALS?
mutations in neurofilaments (intermediate filaments in the neurons)
Abnormal growth/accumulation of neurofilaments?
progressive loss of motor neurons> muscle atrophy, paralysis, death
A patient does something to cause blistering and cell separation with the slightest touch. What may cause this?
What is the actual dysfunction?
EBS (epidermolysis bullosa simplex)
Desmosomes-keratin- cell structural stability-tearing/shearing forces- intermediate filaments
What end does microfilaments add on to in G actin? What end does microtubules assemble from?
Actin-the plus end
Microtubules- Both ends at different rates–can reorganize
What 3 structures of actin (examples)
Parallel bundles (Mv), Contractile bundles (focal adhesions), Networks (cell cortex- shape/movement)
Myosin I and myosin II. functions
1- membrane vessicles/cargo shipping
2- muscle movement
Microfilaments (actin)
Intermediate filaments (Keratin)
Microtubules (tubulin)
Function:
microfilaments- adherens junctions (between cells) & focal adhesions (cell to ECM)
Intermediate filaments- desmosomes (cell-cell) & hemidesmosomes (cell-ECM)
Microtubules- MTOC cell division
Cytoplasmic microtubules. What might happen with dysfunction?
mitotic spindles & spacial trafficking of vesicles and other organelles.
Cells won’t divide correctly-
Chromosomes may not separate correctly
Organelles may not be able to go where they need to go
Axonemal microtubules
Central axoneme shaft of cilia and flagella
Microtubule growth
heterodimers of a/b tubulin bound to GTP bind to either end of growing MT.
-Occurs faster at PLUS end where GTP-tubulin concentrations high.
If rate is slow- GTP hydrolysis catches up and tip favors depolymerization (catastrophe)
MTOC
Neg end anchored to MTOC-Pos extends out-site of NUCLEATION
Centrosome=two centrioles in pericentriolar material
Colchicine
Inhibits MT growth-inhibits neutrophils to reduce gout inflammation.
Vincristine/vinblastine
causes tubulin aggrigation-block tumor cell growth
Paclitaxel (taxol)
microtubules stuck in mitosis- block tumor cell growth
Kinesin & Dynein. What might happen in dysfunction?
“dine in” “in towards the center neg end)
Microtubule dependent motor proteins
Kinesin-vesicles toward Pos end (periphery)
Dynein-transport vesicles central to Neg end
Uses ATP.
dysfunction-intercellular transport may be disrupted?
KARTAGENER SYNDROME
“kindergardner syndrome- dying b/c of school”
No Dynein in microtubules: flagella (sperm) and cilia (respiratory) resulting in male sterility and chronic respiratory infections
If the TGN has dysfunction what might happen? What won’t be affected?
- protein sorting intracellular or extracellular destinations will have problems. constitutive/regulatory secretion may be affected.
- Post-transcriptional processing (glycosylation, proteolysis etc) happen throughout the golgi and probably won’t be affected
Proteins residing in the cell are marked with ___ sequence.
KDEL (lys-asp-glu-leu) on the C terminus of the protein.
Constitutive exocytosis
default-(ie: albumin, membrane proteins nakatpase, sphongolipids)
regulated exocytosis
ALWAYS mediated by Ca signaling.
ie- hormones (insulin, glucagon), NTM (epinephrine, acetylcholine), digestive enzymes
Pathway of Lysosomal enzymes/proteins that stay in the the lysosome.
tq: What could happen if no M6p? what happens if no receptor.
add M6P in golgi->calthrin coat & receptor-dep transport to endosome- P removed in acid cytosol of endosome-m6p receptor recycled back to Golgi for reuse.
Icell disease
I-cell disease- POST TRANSLATIONAL-Genetic
deficiency of enzyme that adds M6P to lysosomal proteins in TGN. (endosomes can’t become lysosomes_) leads to buildup of macromolecules that should have been degraded by lysosomes.
Pathology:
- Developmental delays
-Short-trunk/dwarfism
-lethal by 7yrs (congestive heart failure or respiratory tract infections)
Increased lysosomal proteins in the blood and identification of inclusion bodies at LM
I-Cell Disease
- phosphotransferase dysfunction in golgi
- lysosomal enzymes don’t get M6P Tag/Label & exocytose via Golgi default pathway.
- accumulation of molecules inside lysosomes waiting for degradation
Lysosomal diseases
Most- fail to degrade molecules- dysfunction of lysosomal hydrolases (~50 genetic diseases)
ICELL & others affect biogenesis of lysosomes (icell interrupts vesicular transport).
2 lysosomal storage disorders/enzymopathies of degradation & their disorders respectively
Sphingolipidosis (neimann-pick, tay-sachs, gaucher)
Mucopolysaccharidosis (huler,hunter)
Neimann-Pick disease. What kind of disease?
enzyme deficiency and accumulation?
Sphingomyelinase Enzyme deficiency-
accumulating sphingomyelin
dysfunctional metabolism of sphingolipids (found in cell membranes)
Deficiency in degrading sphingolipids, glycosaminoglycans, and glycogen
dysfunction degrading sphingolipids (Tay-sachs, Neimann-Pick, gaucher).
Diseases of degrading GAG’s (Huler, Hunter)
Glycogen (Pompe’s syndrome)
Sphingolipids
- Signal transduction and cell recognition
- Derivatives of ceramide (sphingosine FA esterification)
- localized in CNS white matter
- Hereditary defects in lysosomal enzymes that break down sphingolipids cause sphingolipidoses (lysosomal storage diseases) Tay-sachs, gauchers, nieman-pick
Tay-Sachs disease
- Hexosaminidase A enzyme deficiency
- GM2-ganglioside Accumulates
-Retinal red dot-autosomal recessive- no cure/treatment-nerve cell death in brain.
Gaucher disease
B-Glucosidase deficient- glucosylceramide accumulates- large liver/spleen- sphingolipidosis
Hurler Syndrome
Mucopolysaccharidosis
Iduronidase deficient;
Heparan sulfate/dermatan sulfate accumulates
Hunter Syndrome
Mucopolysaccharidosis
