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Langmuir Trough
-used an experiment w/ pressure and proposed that a cell membrane could be a phospholipid bilayer (as opposed to monolayer)
-1917
Danielle and Davson
first formal model of a cell membrane
-1935
-protein-phospholipid-protein sandwich with a polar pore lined w/ proteins
what is the significance of the J.D. Robertson model?
-used TEM
-confirmed D/D model
-found OsO4 on the membrane
-suggested glycosylation
1960's/1970's 4 critical experiments...what were they?
1) Freeze fracture- Dan Branton
2) Cell fusion
3) Cell patching/capping
4) FRAP
Freeze fracture by Dan Branton
-he was the 1st developer of FF
-they used a RBC and FFed it and found mosaic of bumps
-discovered transmembrane proteins
fluid mosaic model
A model that describes the structure of cell membranes. In this model, a flexible layer made of lipid molecules is interspersed with large protein molecules that act as channels through which other molecules enter and leave the cell.
FRAP using con a
binds to carb groups
50% of proteins migrated
endoplasmic vs cytoplasmic
endo cytoplasmic
outside inside
glycosylated non glycosylated
RBC ghost
inside out rbc
why are RBC's the best cell type
plentiful
easy target
easy to seperate
membranes are simple
spectrin
rbc dimer
binds to glycophorin
cytoskeleton proteins that line the intercellular part of the cell membrane.
fibrous tetramers
ankyrin
binds to spectrin
asymetric distribution of phospholipids is apparent because?
outer and inner leaflets (lipid bilayers)
phosphoglycerides
cytoplasmic leaflet
in cancer it's an endoplasmic leaflet
3 types of phospholipids
phosphoglycerides, sphingolipids, cholesterol
flippase
transmembrane lipid transporter fluorochromes
quenchers
enzyme that flips phospholipids from exoplasmic faces
sphingolipid/sphingomyelin
main component of myelin
sterols
steoid alchohols
3 kinds of plasma membrane proteins
integral membrane proteins, lipid anchored proteins, peripheral proteins
integral membrane proteins
permanently attached to the biological membrane
not easily washed off
lipid anchored protein
A type of integral membrane protein that is attached to the membrane via a lipid molecule.
can wash off
anchored to lipids
peripheral proteins
Protein appendages loosely bound to the surface of the membrane and not embedded in the lipid bilayer.
easily washed off
bacteriorhodopsin
integral membrane protein
transports protons across cytoplasmic membrane
serpentine
800 diff types
4% of proteins
-signaling
CPR family
G protein coupled receptors
G protein coupled receptors
A signal receptor protein in the plasma membrane that responds to the binding of a signaling molecule by activating a G protein. indirectly activate protein kinase enzymes
glycophorin
rbc
carries sugar molecules, heavily glycosylated
integral mem prot
single pass dimer
trans mem domain has hydrophobic AR
hydrophillic charged coat
receptor mediated endocytosis
receptor-ligand interaction. Receptors on the plasma membrane of the target tissue will specifically bind to ligands on the outside of the cell.
LDL
low density lipoprotein (carries cholesterol)
ligand
A molecule that binds specifically to another molecule, usually a larger one.
coated pits
regions of the cell membrane specialized in receptor-mediated endocytosis.
ldl is relased at ph of?
idk but it's acidic
founder effect class I
LDL-R isn't synthesized
transport defect
LDL isn't properly transported
binding defects
LDL is not properly bonded
founder effect class IV
LDL doesn't cluster properly
recycling defect
LDL does not properly recycled
adherens junction
a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. Protein complexes that occur at cell-cell junctions in epithelial and endothelial tissues, usually more basal than tight junctions
desmosomes
a structure by which two adjacent cells are attached, formed from protein plaques in the cell membranes linked by filaments.
steroid hormone receptors
internal receptor that turns on specific genes when it is activated by binding a signal molecule. found in the nucleus, cytosol, and plasma membrane of target cells.
ferrotransferrin system
controls the level of free iron (Fe), augments iron update
receptor tyrosine kinase(RTK) mutations and general amount of rtks
100
most are linked to cell division (mutation can = cancer)
receptor tyrosine kinase(RTK)
high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones.
IP3 triggers the release of
intracellular calcium
IP3/DAG
2nd Messenger
Smooth muscle contraction by horm/NT
GnRH, Oxytocin, ADH (V1-receptor), TRH,
Histamine (H1-receptor), Angiotensin II,
Gastrin
patch clamp
technique in electrophysiology used to study ionic currents in individual isolated living cells
insulin
first prot to be chemically synthesized
-binds to receptor(glucose enters cell)
-protein synthesis
-differentiation(stores fat)
cAMP system
effector?
adenylate
studying the cAMP system:
Forskolin
supplement
binds and activates adenylate and increases [cAMP]
studying the cAMP system:
Cholera toxin
gtp cant become gdp
dehydration
studying the cAMP system:
GMP-PNP
non-hydrolyzable and keeps the G-protein. The GPCR system always sees GMP-PNP as GTP
methy xanthides and cAMP
inhibits cAMP frombecoming AMP
cAMP
second messenger
cell specific interactions
activates protein kinase
-in cyto=activation of PKA
RTKs
dimer
stimulates cell division using g proteins
what is transported by
transferrin receptor mediated endocytosis
iron
how does cAMP work in the nucleus
translocation of catalytic unit to nucleus
GPCR
900
receptors
-use g proteins
-1 mono metric g prot
-3 tri metric g prot(most used)(3 steps)
CHO cells
- used to measure glucose transport
db cAMP
membrane solulable analog of cAMP
calcium
used for muscle contraction,action potentials,cell-cell adhesion
ca2+ binds to calmodulin
glutamate causes neurons to increase [Ca2+]
-that can cause seisers if too much
calmodulin
inhibits kinase
can cause cell death
Nitricoxide(NO)
gas
diffuses out of cells to affect adjacent cells
-used for blood pressure (increase[NO]=decrease in blood pressure cuz blood vessels dilate)
protein destinatinos
export
dissolved in cytoplasm
embeded in cell memrane
go to an organelle
keith porter
discovered smooth and rough ER
smooth ER
Ca2+ resivuor
site of fattyacid/phospholipid synthesis
cytoskeleton
detoxification
transport
differentiate proteins
RER post translational translocation
-prot with signal recognition particle attaches
-protein synthesis recommences
-signal sequence is cleaved
-protein goes to the lumen
where are most multimuric proteins assembled?
RER
what RER proteins are critical to assembly?
PD!
BiP(chaperone)
calneticulin
endoplasmic reticulum can check protein validity
how do RER vesicles find their target?
Vsnare and Tsnare