CHAP 14: PLASMA MEMBRANE

cell and molecular

What is the structure of the membrane that carries out specific functions?

Phospholipid bilayer

What is a good model for studies of membrane structure?

Plasma membranes of mammalian red blood cells (erythrocytes)

• don’t have nuclei or internal organelles

How do you see the bilayer structure of erythrocyte plasma membrane?

High-magnification electro micrograph

• railroad track appearance

IN the plasma membrane, how are phospholipids distributed in the inner and outer leaflets?

They are asymmetrically distributed

What are the 5 main phospholipids in animal cells?

Phosphatidycholine, Phosphatidylethanolamine, Phosphatidylserine, Phosphatidylinositol, & Sphingomyelin

Percentage In the plasma membrane, what is the percentage of lipids that the 5 major phospholipids account?

50%

In the outer leaflet of the membrane bilayer, what phospholipid does it mainly consist of?

Phosphatidylcholine and sphingomyelin

What phospholipids are predominantly in the inner leaflet of the plasma membrane?

Phosphatidyletholamine & Phosphatidylserine

Where is Sphingomyelin synthesized?

Lumenal surface of the GOLGI membrane

• determines location on the EXTRACELLULAR SIDE OF THE PLASMA MEMBRANE (outer leaflet)

Where are the other phopshoplipids synthesized (non sphingomyelin)?

At the cytoplasmic leaflet of the ER membrane then distributed symmetrically to the cytosolic and lumenal sides of the membrane

What is the charge of the phosphatidylserine head?

negative charge

• predominant in the inner leaflet = net negative charge on the cytosolic side of the plasma membrane (inside membrane)

What are the lipids on the outer leaflet of the plasma membrane?

Sphingomyelin, glycolipid, phosphatidylcholine, cholesterol

What are the lipids on the inner leaflet of the plasma membrane?

Phosphatidylserine, Phosphatidylinositol, Phosphatidylethanolamine

Plasma membrane of animal cells have what other than phospholipids?

Glycolipids + cholesterol

Where are Glycolipids synthesized?

In the Golgi

Cholesterol has higher affinity for what phospholipid in the outer leaflet?

Higher affinity for Sphingomyelin

What is the 2 general features of lipid bilayers?

1. Phospholipid structure is responsible for the barriers between 2 aqueous compartments (((membrane is impermeable to water-soluble molecules)

2. Bilayers of naturally occuring phospholipids are viscous fluids and not solids

   1. long H-C chains of lipids move freely in the interior of the membrane, so the membrane is flexible; lipids + transmembrane proteins are able to diffuse laterally within the membrane 

Fatty acids that have 1/more double bonds are called

Unsaturated fatty acids

If there are more unsaturated fatty acids in a membrane… then the membrane is

more fluid

Cholesterol and Sphingolipids ( sphingomyelin and glycolipids) cluster called

Lipid Rafts

Percentage of most plasma membrane consistence

50% lipids, 50% proteins + carbohydrates (glycoproteins +lipids, 5-10%)

What is the fluid mosaic model

2-d fluids with proteins inserted into the lipid bilayers

• fluid: PROTEINS FLOAT , SEA OF LIPIDS

• mosaic: variety of proteins are embedded into the plasma membrane

PROTEINS + LIPIDS ARE ABLE TO DIFFUSE LATERALLY

Which protein will be easy to remove from the membrane?

Peripheral proteins

What are Peripheral Membrane proteins indirectly associated with?

protein-protein interactions like ionic bonds and peripheral membranes can be disrupted by polar reagents

• SOLUBLE IN AQUEOUS BUFFERS

How can integral membrane proteins disassociate only by 

reagents that disrupt hydrophobic interactions;; AKA DETERGENTS

• amphipathic molecules containing hydrophobic and hydrophilic groups

• the hydrophobic portions of detergents displace the membrane lipids + bind to the hydrophobic portions of the integral membrane proteins

• detergent-protein complexes are soluble in aqueous solutions

What is the detergent-protein complex from the integram membrane?

Hydrophobic tails of the detergent bind to the hydrophobic regions of the integral membrane —> soluble aqueous solution 

Integral proteins span membrane with what type of regions

alpha

Integreal proteins are what type of proetins?

Transmembrane proteins (span on both sides of the membrane)

How many helices of amino acids do transmembrane proteins insert?

20-25 hydrophobic amino acids inserted into the membrane of the ER during synthesis of the popypeptide chain

What is the way proteins are transported to the plasma membrane?

TRANSPORTED in vesicles from ER —> GOLGI —> Plasma membrane

When transmembrane proteins are in transport to the plasma membrane what is added on them?

Glycoproteins w/oligosaccharides on the surface of the cell

What makes up cortical cytoskeletons?

peripheral membrane proteins (are compoennts of the cortical cytoskeleton)

Where is the Cortical cytoskeleton?

It is under the plasma membrane and determines cell shape

What is the most abundant peripheral membrane protein of red blood cells?

Spectrin

• major cytoskeleton protein of erythrocytes

What are other peripheral membrane proteins of rbcs?

Actin + ankyrin

• Ankyrin: link between plasma membrane and cytoskeleton by binding to both spectrin + integral membrane protein band 3

What does protein 4.1 do?

It is an additional link between the membrane and cytoskeleton, which binds to junctions of spectrin and actin _ glycophorin 

What are the 2 main integral membrane proteins of RBCS

Glycophorin + band 3

What is Glycophorin?

Small glycoprotein of 150 amino acids, and crosses the membrane with a single membrane spanning ALPHA HELIX of 23 amino acids

• glycosylated 50% carbohydrate + glycosylated amino-terminal

What is Transmembrane protein of RBCs BAND 3

anion transporter responsible for BICARBONATE AND CLORIDE IONS through the RBC membrane 

• band 3 polypeptide chain is 911 amino acids 

• 14 membrane spanning ALPHA HELICAL RELGIONS 

  • WHEN IN THE MEMBRANE: DIMERS OF BAND 3 FORM GLOBULAR STRUCTURES

How is the attachment of some proteins anchored to the plasma membrane?

Covalently attached lipids

PROTEINS THAT are anchored in the plasma membrane is by 

Through GPI ANCHORS

• GPI anchors are added to certain proteins that have been transferred into the ER and are initally anchored in the membrane by a C-terminal transmembrane region

• the transmembrane region is cleaved as the gpi anchor is added —→ proteins are attached to the membrane only by the glycolipid

What is a GLYCOALYX?

It is the surface of the cell covered by a carbohydrate coat, which is formed by oligosaccharides of glycolipids and glycoproteins

• protects the cell surface from ionic and mechanical stress

• forms barrier to invading microorganisms

• cell-cell interactions

What are the lipid anchor proteins?

RAS and SRC : found in phospholipids

Where are RAS and SRC translated?

free ribosomes they are translated

Ammendments to the fluid mosaic model include:

Mobility of many plasma membrane proteins are restricted 

• Membranes are composed of different domains that have different functions and roles 

  • epithelial cells: polarized because the plasma membranes are divided into apical and basolateral domains

What are Caveolae

They are small lipid rafts that start as invaginations of the plasma membrane organized by the CAVEOLIN

What does Caveolin interact with? (membrane protein)

Cholesterol ( high amount needed for caveolae)

What do Caveolae do?

• Endocytosis

• Cell signaling

• Regulation of lipid transport

• Protection of plasma membrane against mechanical stress

  • Found in half of the plasma membrane in cells:

  • muscle cells, adipocytes, epithelial cells

What mantains the shape of caveolae?

Caveolin + Cavins 

What disease is caused by mutations of Caveolae?

Prions

What are the 2 main ways molecules are transported?

Passive and Active

What is facilitated diffusion?

It is the movement of molecules through the facilitation of transmembrane proteins without external source of energy (helps charged and polar molecules like carbs, amino acids, nucleosides, and ions) go through the plasma membrane without interaction of hydrophobic interior 

What are the 2 protein types that mediate in facilitated diffusion?

Carrier and channel proteins

What are channel proteins?

Bind specific molecules to be transported on 1 side of the membrane then conformational change creates the molecules to pass through the membrane and be released

What are channel proteins:

They form open pores through the membrane allowing free diffsuion of any molecules 

What are Ion Channels

Mediate the passage of ions across the plasma membranes

• not permanently opened, opened by gates

What did the human and the mouse cells prove when they fused to produce hybrid cells?

It showed mobility of membrane proteins

Chloride is higher inside or outside the cell?

Chloride is higher outside the cell

Na+ is higher inside or outside the cell?

Na+ is higher outside of the cell

Is K+ higher outside or inside the cell?

K+ is Higher inside the cell

What are Ligand-gated channels:

These channels open when there is binding of neurotransmitters or other molecules 

What are voltage-gated channels?

These channels open when there are changes in electric potential across the plasma membrane

In the Na+K+ pump, what is the exchange?

3 Na+ out and 2 K+ in

Which molecule is bigger Na+ or K+?

K+ is bigger

In the Na+K+ Pump, is it passive or active transport?

This Na+K+ pump is active transport

• atp hydrolysis

In the Na+K+ pump, what is the mechanism`

1. 3 na+ bind inside the cell 

2. ATP phosphorylation

3. 3 Na leave the cell

4. 2 K+ from outside the cell bind in the the sites

5. dephosphoylation 

6. 2K in cell

Is there more Calcium inside or outside the cell?

There is more calcium outside the cell

What is the Ca+2 H+ Pump?

Powered by ATP hydrolysis

1. Ca+2 is pumped from cytosol OR IN ER LUMEN out of the cell (low ca+2 in the cell)

2. Moves H+ into the cell

2 Ca+2 out 2H in 

WHAT ARE ABC TRANSPORTERS

2 transmembrane subunits with alpha helices and 2 atp binding domains 

• in prokaryotes + eukaryotes

• bacteria: exporters + importers

• human: exporters - toxins

ABC TRANSPORTERS were expressed at high levels in cancer cells

• MDR: remove toxic foreign compounds from the cells

• CFTR: transports CL actively and driven by ATP

Where are H+ ATPASE pumps present?

On lysosome membranes

How were early endosomes formed?

Fusion of various vesicles through the H+ATPASe

What is endocytosis?

Material that will be ingested is surrounded by area of plasma membrane, then buds off inside the cell

What is phagocytosis?

Cell eating (cell engulf large particles like bacteria)

What is a phagosome?

It is a large intracellular vesicle with the particles within the vescicle

What is a phagolysosome?

Phagosome + lysosome (digested by lysomal acid hydrolases)

In mammals what are the 2 types of WBCs that are called “professional phagocytes”?

1. macrophages

2. neutrophils

What do macrophages do?

eliminate dead cells and microorganisms 

• agranulocytes

What do neutrophils do?

Neutralize microorganisms and eliminate microorganisms

What is macropinocytosis?

Uptake of extracellular fluids 

What is Clathrin mediated endocytosis? (receptor mediated)

Selective uptake of specific macromolecules that concentrate in clathrin coated pits

• LDL RECEPTORS

• VERY SELECTIVE

• endo product is an endosome —> lysosome

What are clathrin coated pits?

specialized regions of the plasma membrane that macromolecules internalize and first bind to the receptors

What are interanlization signals:

amino acid seuqneces in the cysosolic domain of the receptors

• BIND CLATHRIN ON THE CYTOSOLIC SIDE OF THE MEMRBRANE

What is the Clathrin coated vesicles?

Clathrin assembles into a basket like strcutrue (invaginated pits) that bud from the membrane

What plays a key role in vesicle budding?

GTP-DYNAMIN

• assembles into rings around the necks of invaginated pits (constrict) driven by hydrolysis of GTP (pinch them off to produce free clathrin-coated vesciles inside the cell)

  • Extracellular fluids incorporate into the vesicles as they bud from the plasma membrane, so clathrin mediated endocytosis is also non selective uptake of extracell fluids

WHAT IS LDL

Low density lipoprotein

• cholesterol is transported through the bloodstream in form of lipoprotein

What did BROWN AND GOLDSTEIN demonstrate that the uptake of LDL by mamillian cells in the lab?

requires the bidning to a cell receptor, that is concentrated in clathrin coated pits

• receptor is recycled to plasma membrane while LDL transported to lysosomes

What does Caveolae do in Clathrin independent endocytosis?

Attach to proteins that help in endocytosis

What is Clathrin Independent Endocytosis?

Does nto involve specific membrane recptors or coated vesicles

• macropinocytosis and internalization of caveolae

What is clathrin’s role?

Gives shape to vesicle

What is clathrin specifically?

It is a “basket” like structure outside the vesicle 

What is ATP SYNTHASE

Mitochondria and chloroplast H+ ions move down the concentration to form ATP

H+ATPASE is in

bacteria, yeast and plant cells

• acidity in gastric fluids: H+ is pumped outside of the stomach lining to create hcl

• in plants: H+ out to sugarin

Clathrin mediated endocytosis was first studied in patients with..

Familial hypercholestermia