Cell membrane 1 Flashcards
What are the basic components of eukaryotic membranes?
Lipid bilayer
Integral and peripheral proteins
Glycocalyx
Cytoskeletal associations
What are the major types of lipids in membranes? Are these lipids amphipathic?
All 4 lipids possess hydrophobic and hydrophillic regions
- Phospholipids- make up the bulk of membrane proteins
- Cholesterol
- Glycolipids
- Phosphatidylinositols
What is the purpose of phospholipids in the plasma membrane?
Establish basic membrane structure.
Can be glycosylated.
What is the purpose of cholesterol in the plasma membrane?
Stiffens membranes.
What is the purpose of glycolipids in the plasma membrane?
Have sugar component. (minor amount in membrane)
What do phosphatidylinostiols do?
Cell signaling (minor amt in membrane)
What do Cystic fibrosis, muscular dystrophy and heridatory spherocytosis have in common?
Faulty membrane functioning due to mutations in, or loss of, certain membrane-associated proteins
What is the function of the membrane?
- Establish specialized environment (boundary between inside and outside of cell, define intracellular compartments)
- Serve as a scaffold to organize protein complexes involved in biochemical behavior
- Semi-permeable barrier
- Transport
- Sensing and responding to environment
- Cell protection and identification
- Cell junctions and adhesion
What two lipids make up the bulk of the membrane?
- Phospholipids (4)- 3 phosphoglycerides and 1 sphingolipid
- Sterol (cholesterol): varies in quantity among membranes, stiffens membrane, reduces permeability, inhibits phase changes
What two lipids make up a minor part of the membrane?
Glycolipids and phosphatidylinositol
What are Glycolipids?
- neutral or negatively charged depending on sugars attached
- Functions: protection (glycocalyx), surface properties of membranes, cell identification, cell adhesion
- Present only on NON-CYTOSOLIC LEAFLET
- may partition into lipid rafts
- Most complex are gangliosides (can serve as entry points for bacterial toxins
DEFICITS: toxic to neurons, basis pof pathology for lysosomal storage disease
What are Phosphatidylinositol phospholipids?
- Inositol sugar which can be phosphorylated at different positions
- Responsible for cell signaling:
stimulation > inositol cleaves DAG and IP3 > DAG activates protein kinase C, phorphorylates target proteins > IP3 binds to SER and opens Ca channels into cytoplasm > binds and modulates fxns of Ca binding proteins
Where are membrane lipids synthesized?
ER: Phosphoglycerides (phosphatidlyethanolamine, phosphatidylserine, phosphatidylcholine)
GOLGI: Sphingomyelin and Glycolipids (made form sphingosine which is synthesized by GA)
How do phospholipids behave in the lipid bilayer?
- Flex, rotate, and are laterally mobile within a leaflet
2. Spontaneous flipping between leaflets is rare
What are the consequences of phospholipid behavior?
- Amphipathic nature prevents movement between monolayers–flippases have evolved that flip phospholipids between leaflets
- Because of lateral mobility within a monolayer, higher order structures are needed to establish membrane domains with a distinct lipid makeup
Why do phospholipids become asymmetrically distributed between monolayers?
- Phospholipids are initially evenly distributed between leaflets in the endoplasmic reticulum (site of synthesis)
- During translocation of membrane to the plasma membrane, flippases selectively flip specific phospholipids so that the bilayer becomes assymetric:
- choline-containing phospholipids (PCholine & Sphingomyelin) are flipped to the non-cytosolic leaflet, resulting in an enrichment of amino
- phospholipids (PEethanolamine & PSerine–negatively charged) in cytosolic leaflet of the plasma membrane.
- LUMINAL SIDE OF ER- glycosylate membrane lipids glycosylate lipids of non-cytosolic leaflet
What are lipid rafts?
- Specialed areas of bilayer composed of specific types of lipids and proteins
- Rich in sphingolipids, cholesterol and certain proteins
- Transport vesicles and involved with signal transduction events
What are integral proteins? How do they behave?
- Span/ embedded in the lipid bilayer, have to disrupt membrane structure to get them out
- Exhibit lateral and rotational movement, anchored/organized to carry out particular fxn
What are peripheral membrane proteins?
Attached to the surfaces of the bilayer or to integral membrane proteins
What is glycocalyx?
- The “cell coat”, the sugar groups covalently attached to membrane proteins
- Restricted to the non cytosolic surface because of the ways membranes are synthesized
- Fxn: Protection, identification, adhesion
What are mechanisms to organize proteins in membranes?
- Self assembly into aggregates
- tethered to extracellular (Integrin, binds to collagen, organizes integrin into patches)
- tethered to intracellular (Glycophorin bound to sub-membranous network of cytoskeletal molecules composed of acatin and spectrin, critical for fxn and elastic properties of RBC)
- Bind to proteins on an adjacent cell- CADHERIN, self associates in the presence of Ca, links cells together
What are cytoskeletal associations and how do they support the plasma membrane?
Cytoskeletal Assocations–an undercoating of actin microfilaments:
- strengthens membrane
- Restricts lateral mobilitly thus establishing distinct domains (SNARE type proteins, molecules establish specific domain for synaptic vesicle docking and fusion)
- forms specialized structures
- Participates in membrane movements/vesicle formation
- Interlinks cytoplasm, membrane, and ECM
What is the RER? Fxn?
1. Organelle in the cell responsible: protein synthesis of membrane luminal and secretory proteins Regulating CA levels in the cell 2. Covered in ribosmes
What is the SER? Fxn?
- Does not have ribosomes attached
2. Synthesizes lipids, metabolizes and detoxifies harmful compounds
Where are ribosomes in the cell?
- Attached to the RER- proteins are inserted into the ER membrane or the lumen
- Free in the cytoplasm
What is a polysome?
Multiple ribosomes that occupy and move along a single mRNA molecule, can synthesize free floating or attached to the membrane
What determines whether a polyribsome becomes attached to an ER membrane or remains free-floating in the cytoplasm?
Info is contained within emerging polypeptide.
- if polypeptide chain has SIGNAL SEQUENCE, polysome will bind to ER. Polypeptides are spooled through pore forming proteins called the SEC61 complex of the RER.
- absence of SIGNAL SEQUENCE polyribosome remains free floating, and newly formed proteins are released into the cytosol
What are SRPs and where are they found? What role does Sec 61 play?
Complexes of proteins and RNA, recognize and bind polypeptides with exposed signal sequences in ER
-Receptors in ER membrane bind mrna ribosme srp comlex and transfer them to protein translocator, SRP is displaced
What are start/stop sequences?
Determines the relationship of the protein with the membrane. They can exist as a single copy or as multiple copies throughout the polypeptide. Can exist in different orientations
What is glycosylation? What are the 2 major patterns? What are the functions of glycosylation?
- The covalent linkage of an oligosaccharide to certain amino acids.
- The 2 major patterns:
N linked: attached to asparagine–assembled on membrane lipid (dolichol) then transfered to polypeptide chain, most proteins made in ER, sugar groups of these glycoproteins are almost always located on non-cytosolic side of membranes
O linked: attached to serine or threonine, cytoplasmic, sugars added one at a time by glycosyltransferases - Functions:
Protein folding
cell transport
protection
cell signaling
How do proteoglycans compare to other glycoprotiens?
Proteoglycans: o linked, heavily glycosylated, glycosylated in golgi or outside cell, 95% carbs by weight, highly charged GAG typically about 80 sugars long
Other glycoproteins: N linked, glycosylated in ER and modified in Golgi, only a few% carb by weight, numerous short, branched oligosaccharide chains
What are proteasomes? Where are they located?
Proteosomes are proteins that ubiquinate and destroy misfolded proteins.
Located in cytoplasm
What are the two proteins involved in quality control of protein synthesis?
Chaperones and proteasomes
What happens to misfolded proteins?
Misfolded ER prtoeins are transported from ER to cytoplasm by membrane translocase for ubiquitylation, signals proteasome, proteasome chew it up.
What are chaperones and how do they relate to protein synthesis?
Help nascent proteins fold correctly (in cytoplasm and ER)
What are the responses to misfolded proteins in a cell?
- Heat shock response: misfolding in cytoplasm, leads to increased expression of cytosolic chaperones to facilitate refolding
- Unfolded proteins response: misfolded proteins in ER, increased expression of: ER chaperones to help refold, genes involved in tetrotranslocation and proteasomal degraddation, there is also some suppression of further protein synthesis
What are the sensors for misfolded proteins and how do they activate genes to increase protein folding capacity of ER?
- IRE1: Kinase that recognizes misfolded proteins in ER, Regulates mRNA splicing and initiates translation of proteins that help with protein folding
- PERK: Inhibits translation initiation factor reducing proteins entering ER and suppresses over all protein synthesis, increases production of chaperones
- ATF6: Regulates proteolysis release
How is Ca used to regulate the cell?
Cells normally keep cytosolic Ca low, ER membrane have Ca transporters that actively transport Ca into ER lumen, ER membrane also have Ca channels that can release Ca from lumen into the cytosol under appropriate stimulation
Where does detoxification occur and what enzyme carries it out?
Most in SER by cytrochrome p450
Enzymes makes foreign compounds more hyrdophillic so they can be released into the bloodstream and eliminated by the kidneys
