Chapter 11 Biological Membranes and Transport

caveolae

(Latin for "little caves"; singular, caveola), which are a special type of lipid raft, are small (50-100 nanometer) invaginations of the plasma membrane in many vertebrate cell types, especially in endothelial cells and adipocytes.

FRAP

(fl uorescence recovery after photobleaching): A technique used to quantify the diffusion of membrane components (lipids or proteins) in the plane of the bilayer.

Kt (Ktransport)

A kinetic parameter for a membrane transporter analogous to the Michaelis constant, Km, for an enzymatic reaction. The rate of substrate uptake is half-maximal when the substrate concentration equals the Kt.

selectins

A large family of membrane proteins, lectins that bind oligosaccharides on other cells tightly and specify dally and serve to carry signals across the plasma membrane.

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.

GPI-anchored protein

A protein held to the outer monolayer of the plasma membrane by its covalent attachment through a short oligosaccharide chain to a phosphatidylinositol molecule in the membrane

ATP synthase

An enzyme complex that forms ATP from ADP and phosphate during oxidative phosphorylation in the inner mitochondrial membrane or the bacterial plasma membrane, and during photophosphorylation in chloroplasts.

positive-inside rule

General observation that most plasma membrane proteins are oriented so that most of their positively charged residues (Lys and Arg) are on the cytosolic face.

ABC transporters

Plasma membrane proteins with sequences that make up ATPbinding cassettes; serve to transport a large variety of substrates, including inorganic ions, lipids, and nonpolar drugs, out of the cell, using ATP as the energy source.

multidrug transporters

Plasma membrane transporters in the ABC transporter family that expel several commonly used anti tumor drugs, thereby interfering with antitumor therapy.

t-SNAREs

Protein receptors in a targeted membrane (typically the plasma membrane) that bind to v-SNAREs in the membrane of a secretory vesicle and mediate fusion of the vesicle and target membranes.

v-SNAREs

Protein receptors in the membrane of a secretory vesicle (typically the plasma membrane) that bind to t-SNAREs in a targeted membrane (typically the plasma membrane) of a secretory vesicle and mediate fusion of the vesicle and target membranes.

amphitropic proteins

Proteins that associate reversibly with the membrane and thus can be found in the cytosol, in the membrane, or in both places.

transporters

Proteins that span a membrane and transport specify c nutrients, metabolites, ions, or proteins across the membrane; sometimes called perm eases.

Na+ glucose symporters

The Na+ is traveling down its concentration gradient. However, in order for the Na+ to be transported into the cell by the symport, a molecule of glucose must be transported at the same time. The intracellular concentration of Na+ is kept low by the Na-K ATPase which is an active transport protein.

membrane potential (Vm)

The difference in electrical potential across a biological membrane, commonly measured by the insertion of a microelectrode. Typical membrane potentials vary from 225 mV (by convention, the negative sign indicates that the inside is negative relative to the outside) to greater than 2100 mV across some plant vacuolar membranes.

Na+ K+ ATPase

The electrogenic ATP-driven active transporter in the plasma membrane of most animal cells that pumps three Na outward for every two K moved inward.

electrochemical potential

The energy required to maintain a separation of charge and of concentration across a membrane.

simple diffusion

The movement of solute molecules across a membrane to a region of lower concentration, unassisted by a protein transporter.

electrochemical gradient

The resultant of the gradients of concentration and of electric charge of an ion across a membrane; the driving force for oxidative phosphorylation and photophosphorylation.

scramblases

These are proteins that move any membrane phospholipid across the bilayer down its concentration gradient (from the leaflet where it has a higher concentration to the leaflet where it has a lower concentration); their activity is not dependent on ATP. Scramblase activity leads to controlled randomization of the head-group composition on the two faces of the bilayer. The activity rises sharply with an increase in cytosolic Ca2 concentration, which may result from cell activation, cell injury, or apoptosis; as noted above, exposure of phosphatidylserine on the outer surface marks a cell for apoptosis and engulfment by macrophages. Finally, a group of proteins that act primarily to move phosphatidylinositol lipids across lipid bilayers, the phosphatidylinositol transfer proteins, are believed to have important roles in lipid signaling and membrane trafficking.

voltage-gated channel

a class of transmembrane proteins that form ion channels that are activated by changes in electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, regulating their opening and closing.

bilayer

a film two molecules thick (formed, e.g., by lipids), in which each molecule is arranged with its hydrophobic end directed inward toward the opposite side of the film and its hydrophilic end directed outward.

vesicle

a small fluid-filled bladder, sac, cyst, or vacuole within the body.

channels

a specific macromolecular protein pathway, with an aqueous "pore," which traverses the lipid bilayer of a cell's plasma membrane and maintains or modulates the electrical potential across this barrier by allowing the controlled influx or exit of small inorganic ions

ionophore

a substance that is able to transport particular ions across a lipid membrane in a cell.

micelle

an aggregate of molecules in a colloidal solution, such as those formed by detergents.

porin

any of a class of proteins whose molecules can form channels (large enough to allow the passage of small ions and molecules) through cellular membranes.

ligand-gated channel

are a group of transmembrane ion channel proteins which open to allow ions such as Na+, K+, Ca2+, or Cl− to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand), such as a neurotransmitter.

P-type ATPases

are a large group of evolutionarily related ion and lipid pumps that are found in bacteria, archaea, and eukaryotes.

aquaporins (AQPs)

are integral membrane proteins from a larger family of major intrinsic proteins (MIP) that form pores in the membrane of biological cells.

microdomains

are limited areas inside a membrane that contain different lipid buildups. One common form of a microdomain, for example is a cholesterol enriched area which is also known as a "Raft". A typical lipid raft, seen in the middle of the membrane (Jmol)

floppases

are members of the ABC transporter family described on page 413, all of which actively transport hydrophobic substrates outward across the plasma membrane.

peripheral proteins

are membrane proteins that adhere only temporarily to the biological membrane with which they are associated. These proteins attach to integral membrane proteins, or penetrate the peripheral regions of the lipid bilayer.

permeases

are membrane transport proteins, a class of multipass transmembrane proteins that facilitate the diffusion of a specific molecule in or out of the cell by passive transport.

nicotinic acetylcholine receptor

are neuron receptor proteins that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs, including the nicotinic receptor agonist nicotine.

ion channel

are pore-forming membrane proteins whose functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume.

fusion protein

are proteins created through the joining of two or more genes that originally coded for separate proteins.

rafts

are regions of the membrane bilayer enriched in sphingolipids, sterols, and certain proteins, including many attached to the bilayer by GPI anchors. The -adrenergic receptor is segregated in rafts that contain G proteins, adenylyl cyclase, PKA, and a specific protein phosphatase, PP2, which together provide a highly integrated signaling unit. By segregating in a small region of the plasma membrane all of the elements required for responding to and ending the signal, the cell is able to produce a highly localized and brief "puff" of second messenger.

flippases

are transmembrane lipid transporter proteins located in the membrane responsible for aiding the movement of phospholipid molecules between the two leaflets that compose a cell's membrane (transverse diffusion, also known as a "flip-flop" transition).

V-type ATPases

couple the energy of ATP hydrolysis to proton transport across intracellular and plasma membranes of eukaryotic cells. It is generally seen as the polar opposite of ATP Synthase because ATP Synthase is a proton channel that uses the energy from a proton gradient to produce ATP.

annular lipid

epresent a select set of lipids or lipidic molecules which preferentially bind or stick to the surface of membrane proteins in biological cells.

liquid-disordered state (ld)

fluid state, acyl chains undergo much thermal motion and have no regular organization. The state of membrane lipids in biological membranes is maintained somewhere between these extremes.

F-type ATPases

found in bacterial plasma membranes, in mitochondrial inner membranes (in oxidative phosphorylation, where it is known as Complex V), and in chloroplast thylakoid membranes.

electroneutral

having no net electric charge

major facilitator superfamily (MFS)

is a class of membrane transport proteins that facilitate movement of small solutes across cell membranes in response to chemiosmotic gradients.

Beta barrel

is a large beta-sheet that twists and coils to form a closed structure in which the first strand is hydrogen bonded to the last. Beta-strands in beta-barrels are typically arranged in an antiparallel fashion.

lactose transporter

is a membrane protein which is a member of the major facilitator superfamily. Lactose permease can be classified as a symporter, which uses the proton gradient towards the cell to transport β-galactosides such as lactose in the same direction into the cell.

passive transport

is a movement of biochemicals and other atomic or molecular substances across cell membranes without need of energy input.

integral proteins

is a type of membrane protein that is permanently attached to the biological membrane. All transmembrane proteins are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a significant fraction of the proteins encoded in an organism's genome.

uniport

is an integral membrane protein that is involved in facilitated diffusion. They can be either ion channels or carrier proteins. Uniporter carrier proteins work by binding to one molecule of substrate at a time and transporting it with its concentration gradient.

symport

is an integral membrane protein that is involved in the transport of many differing types of molecules across the cell membrane. The symporter works in the plasma membrane and molecules are transported across the cell membrane at the same time, and is, therefore, a type of cotransporter.

antiport

is an integral membrane transport protein that simutaneously transports two different molecules, in opposite directions, across the membrane. The example below depicts the process by which HCl is secreted into the lumen on the stomach.

BAR domain

is banana shaped and binds to membrane via its concave face. It is capable of sensing membrane curvature by binding preferentially to curved membranes. BAR domains are named after three proteins that they are found: Bin, Amphiphysin and Rvs.

cotransport

is the name of a process in which two substances are simultaneously transported across a membrane by one protein, or protein complex which does not have ATPase activity.

facilitated diffusion

is the process of spontaneous passive transport (as opposed to active transport) of molecules or ions across a biological membrane via specific transmembrane integral proteins.

hydropathy index

of an amino acid is a number representing the hydrophobic or hydrophilic properties of its sidechain. It was proposed in 1982 by Jack Kyte and Russell F. Doolittle. The larger the number is, the more hydrophobic the amino acid.

liquid-ordered state (lo)

polar head groups are uniformly arrayed at the surface, and the acyl chains are nearly motionless and packed with regular geometry.

electrogenic

producing a change in the electrical potential of a cell.

SERCA pump

resides in the sarcoplasmic reticulum (SR) within myocytes. It is a Ca2+ ATPase that transfers Ca2+ from the cytosol of the cell to the lumen of the SR at the expense of ATP hydrolysis during muscle relaxation.

patch-clamping

technique is a laboratory technique in electrophysiology that allows the study of single or multiple ion channels in cells.

active transport

the movement of ions or molecules across a cell membrane into a region of higher concentration, assisted by enzymes and requiring energy.