Exam1 study guide Flashcards
nuclear transport wiht regards to huntingtons
-this mutation is the addition of a glutamine residue which plays a role in increased huntingtin import into the nucleus
what will we learn from progeria
a lot about aging and cardiovascular disease
importins
chaperon proteins that bind to NLS’s and escort proteins into the nucleus
SINEs
small molecules tht bind to and block the pocket on exportin 1 used by tumor supressor.
-this inhibits cell deivision and is a target for cancer drugs
Key points about export
- NES
- selectivity of an exportin
- exportin 1
- proteins and ribonucleoproteins have nuclear export signals that are recognized by exportins. Exportins recognize a specific 5’-Gppp site on the nuclear pore and bind to it
- each exportin has a selective set of cargos
- exportin 1 is for anti-tumor proteins
nuclear membrane assembly/disassembly
- lamins are responsible for connnecting chromatin to the nuclear membrane
- during interphase, lamins are dephosphorylated, leaving the nuclear membrane intact
- early in mitosis, lamins are phosphorylated by a kinase, causing the chromatin-nuclear mem connection to break and the nuclear membrane to disassemble
- late in mitosis, a phosphotase removes the phosphates from the lamin and the chromatin are allowed to join the nuclear membrane again the membrane itself reforms
Niemann pick
- he thinks this will be the next disease to teach us a lot about lipid trafficking in cells and about other diseases
- it is NOT a sphingolipid disorder, we actually do not know that enzymes and substrated involved yet
plasma membrane composition
-lipid rafts
- asymmetrical
- lipid rafts are more rigid than the rest of the membrane because they are high in sphingolipids and cholesterol. They can move quickly in the membrane and are responsible for concentrating ligand-receptor complexes into clathrin coated pit regions and important for bringing together components of signal transduction pathways
why is an asymmetrical membrane important
-the outer leaflet is generally much more fluid than the inner leaflet, allowing lipid rafts to rapidly concentrate ligand-receptor pairs at specific sites on the membrane for internalization
sphingolipids and fusion
-they do not have fusogenis properties
first LSD to be treated with enzyme replacement therapy
-Fabry’s disease and then Gaucher followed
factors affecting membrane fluidity
- heat
- chain length
- double bonds
- cholesterol
band 3
- the anion exchanger in RBC’s
- this protein has a membrane spanning region, binding sites for ankrin and glycolytic enzymes intracellularly and has an N-links oligosaccharide extracellularly
functions of carbohydrates on the cell surface
- blood type antigens
- pathogen recognition sites
- reservoir for cytokines/growth factors
how particles of different sizes get into the cell
- if it is a bacteria or bigger, it gets in via phagocytosis
- if its a virus or smaller, it gets in via RME (except HIV and measles get in via fusing with the mem)
clathrins
involved in conentrating ligand-receptor complexes into specialized regions of the membrane called clathrin coated pits
lipid rafts
-used to ferry ligand-receptor complexes to the clathrin coated pits
endosomes
-what is created after clathrin coated pits invaginate and pinch off
what must happen for an endosome to fuse with its target?
- it must lose its clathrin coat
- must be acidified by a membrane bound H+ ATPase
- not only does H+ allow fusion but also allows the receptor-ligand complex to seperate
Phagocytosis
-Fc receptors on the surface of the pahgocytic cell recognize IgG moleculse on the particle to be phagocytosed
tuberculosis
this pathogen is phagocytosed
Tangier
- Chesepeak bay, consanguinity
- present with CHD and neurological problems
- swollen bright orange tonsels
- markedly reduced plasma levels of HDL
- gave us a great understanding of CHD
- gene involved is part of the ATP binding cassette fam and responsible for reverse cholesterol transport
- if no LDL comes out of the cell, HDL is cleared to the lymph glands
- LDL that is not cleared builds up in the blood vessel wall
- helped show that the most common lipoprotein defect is reduced HDL
what determines if the protein will be translated on the ER or in the cytoplasm?
- the first 20-25 aa’s which is where the signal peptide resides
- if there is a signal peptide then it will be taken to the ER, if there isnt one, it will stay in the cytoplams for translation
proteins translated in the cytoplasm can go to
- peroxisome
- nucleus
- cytoplasm
- mitochondria
proteins translated on the ER can go to
- ER
- secreted
- plasma membrane
- golgi
- lysosome
I cell disease
- taught us the role of mannos 6 P in targetting the lysosome and led to our current understanding of organeller genesis
- defective enzyme is one which phosphorylates the 6 position of specific mannos residues
- under a microscope, cells with I cell disease appear to have dark, inclusion bodies where the lysosome are filled with biological material
sequences that target proteins to the:
- peroxisome
- nucleus
- lysosome
- mitochondria
- peroxisome: three AA, SKL sequence
- NLS is a 5-6 basic AA sequence
- lysosome: mannose-6-P, this is the only nonpeptide targetting sequence
- mitochondria: a long, 75 AA sequence near the N-terminal end of the protein
