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59 Cards in this Set

  • Front
  • Back

Charles Overton

Confirmed the lipid nature of the cell membrane. - 1895

Julius Bernstein

1902 - Explained the electrolyte interior of cells and the electrolytic potentials in nerve cells.

Irving Langmuir

1917 - Discovered that cell membranes are monolayers or bilayers through the use of a Langmuir Trough

Gorter and Grendel

Used RBCs to extract and measure phospholipids. Under-extracted and undercalculated.




These mistakes cancelled each other out to confirm bilayer.

Mudd and Mudd

Analyzed blood cells:




White blood cells prefer water medium/RBCs prefer more lipid medium

Danielli and Dawson

1935- First model of plasma membrane:


Components:


-phospholipids


-proteins


-pores



J. D. Robertson

1950s


First used TEM to view cell membrane - confirmed the D & D model




Used OsO4 to fix and stain the cells

Freeze Fracture

TEM technique to produce membrane replica.




Bumps proved to be proteins/pores. Liposome control showed smooth surface

Fuse-living cells

Cell fusion experiment with antibodies - must be mouse or human receptor specific.




Concludes some integral proteins can move laterally throughout the "fluid" membrane.

Cell Patching

Add bivalent antibodies to cell. Antibodies will line up -----concludes fluid membrane.

Fluid-mosaic model

Made by Singer and Nicholson - 1972




1) Integral proteins cannot be washed out and are integrated into the cell membrane


2) Peripheral Proteins can be washed off and sit on the surface of the cell membrane

Integral membrane proteins

Single pass - cross the membrane only once


Monomer


Multi-pass - weave in and out of the membrane


Barrel protein - usually used for ion transport


Multi-meric - has more than one protein component

Glycocalyx

Collective carbohydrate groups on the outside of the cell




Con-A labels this

Hydropathy plot

Used to predict the topology of membrane proteins




Membrane spanning region of very hydrophobic amino acids anchor the proteins with non-covalent bonds

Red Blood cells

Cell membrane experiment favorites:


-Easy to get and pruify


-No contaminating membrane/organelles


-Easy to make RBC ghosts (lyse with hypotonic)

Adherins

Purpose: Cell Adhesion


Encircles the cell




Cadherins keep cells together and are Ca2+ dependent; associated with actin cytoskeleton.

Demosomes

Designed for strength and found in epithelial cells.




Intermediate filaments connect desmosomes.

Pemphigus Vulgaris

Autoimmune disease that targets key desmosome protein (Desmogelin 3).




"Unzips" the skin and epidermis peels off.

Tight Junctions

Keeps fluid separated in tissues. Specialized proteins keep fluids out




E.g. bladder, kidney, intestine.




Lanthanum hydroxide/Sodium fluorsein is not membrane soluble and moves up and around cells until tight junction.

Gap Junction

Passes small molecules like cAMP and ions.




Sometimes electrical junctions




Connexon - actual hole in membrane

ATP Pump

Uses ATP to pump ions against gradient.



Uniporter

Pumps one molecule.

Symporter

Cotransporter system.




Moves two molecules in the same direction:


One from high to low, and the other from low to high.

Antiporter

2 molecules in the opposite directions against their gradient.

Autocrine

Ligand is release from cell and received by the same cell receptor.




Cells can become cancerous if self-produces growth hormone.

Paracrine

Ligand is released from one cell and received by another nearby cell.

Endocrine

Ligand is released into the blood stream and reacts with target cells all over the body

Pheramones

Released by one organism and affects another.

Lipid Soluble ligands

Permeable to the cell membrane and has intracellular receptors




Steroids

Lipid insoluble proteins

Need extracellular membrane receptor.




Activates second messenger system.

Ion channel receptor

Very fast acting; ligand binds to receptor and channel is immediately opened.




ex. nicotinic acetlycholine receptor

Receptor Mediated Endocytosis

Delivers ligand into the cell.

Second Messenger Activation

Ligand activates secondary messenger system when bound to receptor.




Cytokines, g-coupled receptors

G-protein Coupled Receptors

Usually interact with

Receptor Tyrosine Kinase

Exists as separate monomers until activation by ligand.




Relies on autophosphorylation for signal transduction.

Forskolin

Activates adenylate cyclase and increases intracellular levels of cAMP

Smooth Endoplasmic Reticulum

Not associated with Protein synthesis; fatty acid and phospholipid syn.




Good for detox (Liver).




High levels of Calcium

Rough Endoplasmic Reticulum

Protein syn. occurs;


Proteins are glycosolated


Formation of disulfide bonds

Where does glycosylation occur?

RER


Cis-Golgi


Medial-Golgi


Trans-Golgi

Type I Integral Protein Synthesis

Requires an internal signal anchor sequence.


Cleaved N-terminal signal sequence.




C-out, N-in




Hydrophobic domain in the middle.




Contain stop-transfer anchor sequence.

Type II Integral Protein Synthesis

No signal sequence is cleaved from the N-terminus




C-in, N-out




hydrophobic domain in the middle




Contain signal -anchor sequence

Type III Integral Protein Synthesis

No signal sequence is cleaved.




C-out, N-in




Hydrophobic tail at N-terminus




Contain signal -anchor sequence

Tail Anchored

C-in, N-out




Hydrophobic anchor at C-terminus

Type IV

Multiple hydrophobic domains.




G-coupled proteins are an example

Protein Disulfide isomerase (PDI)

Oxidizes proteins with thiol groups to form disulfide bonds.




Especially abundant in the ER of liver and kidney.




Can also rearrange disulfide bonds so proteins fold correctly.

Ras G-protein

Signaling molecule within cells involved in activation pathways for cell growth, proliferation and survival.




Over activation leads to cancer.

BiP

Molecular chaperone in the lumen of the ER.




Maintains proteins in unfolded state until ready for folding.




Prevents protein from backsliding through the translocon.

Patch Clamp

Allows the ability to measure the electropotential of a single or multiple ion channel.

Regulated Secretory Pathway

Can store proteins in large electron-dense vesicles.




Dependent on Ca2+ or hormones for release




Release lot of proteins at once

Constitutive Pathway

used for integral membrane proteins. Proteins are not store and released immediately.




Ex. proteins that are synthesized all the time like collagen



Muscarinic acetlycholine receptor

`

HSP Complex

Produced by cells in exposure to stressful conditions such as heat/cold.




Binds to the steroid receptor; often found in the cytoplasm; inhibitory in nature.

Cholera Toxin

Blocks GTP hydrolysis

Earl Sutherland

Discovered the cAMP secondary messengers pathway.

KDEL Peptide

Receptor that prevents protein from being excreted from the RER

The Unfolded Protein Response (UPR)

Activated in a response to accumulated unfolded or misfolded proteins.

Brefeldin A

Can induce the UPR.




Inhibits transport from the RER to the Golgi

Familial hypercholesterolemia

Class I - LDL Receptor not synthesized


Class II - LDL receptor not properly transported to the cell surface


Class III - LDL receptor does not bind to LDL


Class IV - LDL does not properly cluster in endocytosis


Class V - LDL receptor not recycled

Glycophorin

Highly glycosolated protein on the outside of red blood cells which gives them very hydrophilic coat preventing them from sticking to vessels.