Membrane proteins

ninth lecture
membrane proteins

a large fraction of the energy that is consumed by organs such as our brains is used to create ion gradients across membranes. several large families of integral membrane proteins control the movement of ions and other solutes across membranes. chapter 8 introduces three families of pumps that use adenosine triphosphate (atp) hydrolysis as the source of energy to transport ions or solutes up concentration gradients across membranes. for example, pumps in the plasma membranes of animal cells use atp hydrolysis to expel na+ and concentrate k+ in the cytoplasm. another type of pump creates the acid environment inside lysosomes. a related pump in mitochondria runs backward, taking advantage of a proton gradient across the membrane to synthesize atp. a third family, called abc transporters, use atp hydrolysis to move a wide variety of solutes across plasma membranes.

carrier proteins (chapter 9) facilitate the movement of ions and nutrients across membranes, allowing them to move down concentration gradients much faster than they can penetrate the lipid bilayer. some carriers couple movement of an ion such as na+ down its concentration gradient to the movement of a solute such as glucose up a concentration gradient into the cell. carriers generally change their shape reversibly to transport their cargo across the membrane one molecule at a time.

channels are transmembrane proteins with selective pores that allow ions, water, glycerol, or ammonia to move very rapidly down concentration gradients across membranes (chapter 10). taking advantage of ion gradients created by pumps and carriers, cells selectively open ion channels to create electrical potentials across the plasma membrane and some organelle membranes. many channels open and close their pores in response to local conditions. the electrical potential across the membrane regulates voltage-gated cation channels. binding of a chemical ligand opens other channels. for instance, nerve cells secrete small organic ions (called neurotransmitters) to stimulate other nerve cells and muscles by binding to an extracellular domain of cation channels. the bound neurotransmitter opens the pore in the channel. in the cytoplasm, other organic ions and ca2+ can also regulate channels. cyclic nucleotides open plasma membrane channels in cells that respond to light and aromas. inositol triphosphate and ca2+ control channels that release ca2+ from the endoplasmic reticulum.

all living organisms depend on combinations of pumps, carriers, and channels for many physiological functions (chapter 11). cells use ion concentration gradients produced by pumps as a source of potential energy to drive the uptake of nutrients through plasma membrane carriers. epithelial cells lining our intestines combine different carriers and channels in their plasma membranes to transport sugars, amino acids , and other nutrients from the lumen of the gut into the blood. many organelles use carriers driven by ion gradients for transport. most cells use ion channels and transmembrane ion gradients to create an electrical potential across their plasma membranes. nerve and muscle cells create fast-moving fluctuations in the plasma membrane potential for high-speed communication operating on a millisecond time scale, voltage-gated ion channels produce waves of membrane depolarization and repolarization called action potentials.

our abilities to perceive our environment, think, and move depend on transmission of electrical impulses between nerve cells and between nerves and muscles at specialized structures called synapses. when an action potential arrives at a synapse, voltage-gated ca2+ channels trigger the secretion of neurotransmitters. in less than a millisecond, the neurotransmitter stimulates ligand-gated cation channels to depolarize the plasma membrane of the receiving cell. muscle cells respond with an action potential that sets off contraction. nerve cells in the central nervous system integrate inputs from many synapses before producing an action potential. pumps and carriers cooperate to reset conditions after each round of synaptic transmission.
ninth lecture

cellular organelles and membrane trafficking


eukaryotic cells evolved membrane-bounded compartments specialized to provide energy to synthesize lipids, carbohydrates, proteins, and nucleic acids and to degrade cellular constituents. these subcellular compartments, called organelles, have distinctive chemical compositions. organelles vary in abundance and size in different cell types, even within multicellular organisms, in which each tissue and organ has specialized functions. an organelle often holds a monopoly on performing a given task for example, endoplasmic reticulum (er) synthesizes membrane proteins and certain membrane lipids, lysosomes contain enzymes to degrade many macromolecules, and mitochondria convert energy derived from the covalent bonds of nutrients into atp to provide energy for diverse cellular functions.
a semipermeable membrane surrounds each organelle and establishes an internal microenvironment with concentrated enzymes, cofactors, and substrates to favor particular macromolecular interactions. pumps carriers ,and channels in each organelle membrane establish an internal chemical environment (ph, divalent cation concentration, redox potential) that is appropriate for particular biochemical functions. mitochondria and chloroplasts utilize many enzymes embedded in their membranes to catalyze reactions that depend on the separation of reactants across the membrane or involve hydropinghobic substrates and products soluble in the lipid bilayer (. compartments also protect the rest of the cell from potentially dangerous activities, such as degradative enzymes in lysosomes and oxidative enzymes in peroxisomes.
this division of labor among organelles has many advantages but also presents cells with challenges in terms of coordination of cellular activities, organelle biosynthesis, and cell division. organelles are not autonomous, so their activities must be integrated to benefit the whole cell. therefore, mechanisms are required to transport material between compartments and across the membranes that surround them. many functional pathways require macromolecules and lipids to move from one organelle to another in a vectorial manner.

this transport between organelles generally involves budding of vesicles from one membrane-bounded compartment followed by fusion with another, in a process collectively termed vesicular trafficking.

the mechanisms that are used for membrane trafficking. under the direction of membrane-associated gtpases, a coat of proteins from the cytoplasm forms on a donor membrane and distorts the membrane into a vesicle that buds from the surface, carrying the proteins and lipids in the membrane and any material in the lumen. sorting signals direct some proteins into these transport vesicles. cells use three different types of coat proteins for budding from different organelles. after the vesicle moves by diffusion or by active transport along the cytoskeleton to a target membrane, different gtpases and peripheral proteins facilitate fusion of the vesicle with a target membrane. such vesicle traffic moves membranes and content along the secretory pathway from the endoplasmic reticulum to the golgi apparatus, lysosomes, and plasma membrane. retrograde vesicle traffic mediated by other proteins retrieves membranes and proteins from the golgi apparatus back to the er. in spite of this heavy bidirectional traffic between organelles, the sorting mechanisms allow each organelle to maintain its identity.

cells employ at lease five distinct mechanisms to internalize plasma membrane along with a wide range of extracellular materials (chapter 22). ingestion of small particles, including bacteria, takes place by phagocytosis, in which a veil of plasma membrane surrounds the particle and takes it into a vacuole inside the cell. fusion of vesicles containing lysosomal enzymes initiates the degradation of the contents. a second endocytic pathway takes receptors and their ligands into cells in small vesicles coated with clathrin. other forms of endocytosis take up extracellular fluid and patches of plasma membrane enriched in cholesterol, sphingolipids, and certain signaling proteins. inside the cell, the contents and membranes of these various endocytic vesicles are sorted in endosomes for direction in vesicles back to the plasma membrane or onward to the golgi apparatus or lysosomes.

how cells degrade proteins and lipids, some taken in from outside by endocytosis and others from inside the cell. dna is stable, but cells continuously replace most of their other constituents in a cycle of synthesis and degradation. each type of rna, protein, and lipid has a natural lifetime, generally much shorter than that of the cell itself. proteins are degraded and replaced, some every hour, others every day and some every few weeks or months. membrane lipids also turn over some with lifetimes measured in minutes. proteins and lipids taken in by endocytosis are degraded in lysosomes. in the process called autophagy, a double membrane surrounds a zone of cytoplasm, even including entire organelles. fusion of late endosomes and lysosomes with these autophagic vacuoles delivers enzymes that degrade the contents. cytoplasmic and nuclear proteins are degraded by a large protein complex called the proteasome, but only after they are marked for degradation by conjugation with the small protein, ubiquitin. a hierarchy of ubiquitin-conjugating enzymes controls the fate of proteins as they turn over during the cell cycle.


two important processes as they pertain to the biogenesis and functions of the various organelles. the first is the targeting of proteins, either during or after translation to their home organelle. the second is the bidirectional movement of vesicular traffic between organelles and the plasma membrane. the exocytic or secretory pathway from the endoplasmic reticulum to the plasma membrane and lysosomes coordinates organelle biosynthesis and secretion. the endocytic pathway takes in molecules and microscopic particles from outside the cell along with plasma membrane components. operating together, the two pathways coordinate the distribution pathways and turnover of membrane proteins and lipids.

proteins that are synthesized in the cytoplasm either remain there or move to their final destinations in the nucleus (see chapter 14), mitochondria, chloroplasts, and peroxisomes (chapter 18). hundreds of proteins destined for mitochondria and chloroplasts are synthesized in the cytoplasm and directed to these organelles by zip codes built into their polypeptide sequences. most of these guide sequences are removed once the polypeptide has moved through channels into one of the membranes or compartments inside these organelles. different sorts of targeting sequences target dozens of proteins to peroxisomes.