4 5 Membrane Transport and Cell Signaling

4.1 5.1 Cellular membranes

  • Phospholipids:
    • Most abundant lipid in most membranes
    • Amphipathic: has both a hydrophilic region and a hydrophobic region. Bilayer arrangement shelters the hydrophobic tails while exposing the hydrophilic heads to water.

  • Most membrane proteins are also amphipathic:
    • Can reside in the phospholipid bilayer with hydrophilic regions protruding
    • Provides its hydrophobic parts with a nonaqueous environment
  • Fluid mosaic model: the membrane is a mosaic of protein molecules bobbing in a fluid phospholipid bilayer

4.1.0.1 Membrane fluidity:

  • Most lipids and some proteins can shift about laterally:
    • Proteins are much larger and move more slowly
    • Some proteins movie in a directed manner, others can be held in place
  • As temperature decreases, phospholipids become closely packed and the membrane solidifies:
    • Unsaturated hydrocarbon tails cannot pack as closely as saturated tails, membrane remains fluid to a lower temperature
    • Cholesterol helps membranes resist changes in fluidity:
      • Restrains phospholipid movement at high temperatures
      • Hinders close packing at low temperatures
  • Evolutionary differences in membrane lipid composition maintain appropriate fluidity under specific environmental conditions

4.1.0.2 Proteins determine membrane function:

Proteins

Figure 4.1: Proteins

  • Integral proteins: penetrate the hydrophobic hydrophobic interior of the lipid bilayer
    • Transmembrane proteins span the membrane, others extend only partway
    • Some proteins have hydrophilic channels that allow passage of substances (a)
  • Peripheral proteins: not embedded in the lipid bilayer. Loosely bound to the surface of the membrane, often to exposed parts of integral proteins
  • Some membrane proteins are attached to the cytoskeleton or to fibers of the ECM, providing a strong framework for animal cells (c)
  • A single cell may have proteins carrying out several functions, and a single protein may have multiple functions

4.1.0.3 Membrane carbohydrates and cell-cell recognition:

  • Cells recognize other cells by binding to molecules, often containing carbohydrates, on the surface of the plasma membrane (d)
  • Membrane carbohydrates are usually short and branched:
    • Glycolipids: covalently bonded to lipids
    • Glycoproteins: covalently bonded to proteins
  • Function as markers that distinguish one cell from another

4.1.0.4 Synthesis and sidedness of membranes:

  • A membrane has two distinct faces
  • Asymmetric arrangement of proteins, lipids, and attached carbohydrates is determined as the membrane is being built
Synthesis

Figure 4.2: Synthesis

  1. Membrane proteins and lipids are synthesized in the ER
  2. Inside the Golgi apparatus, glycoproteins undergo carbohydrate modification, and some lipids become glycolipids
  3. Synthesized membrane components are transported by vesicles
  4. As vesicles fuse with the plasma membrane, the outside face of the vesicle become continuous with the cytoplasmic face of the plasma membrane. Carbohydrates are positioned on the extracellular face.

4.1.0.5 Concept check

Concept check

  1. The carbohydrates attached to some proteins and lipids of the plasma membrane are added as the membrane is made and refined in the ER and Golgi apparatus. The new membrane then forms transport vesicles that travel to the cell surface. On which side of the vesicle membrane are the carbohydrates?

    They are on the inner side of the transport vesicle membrane.

  2. The soil immediately around hot springs is much warmer than that in neighboring regions. Two closely related species of native grasses are found, one in the warmer region and one in the cooler region. If you analyzed their membrane lipid compositions, what would you expect to find? Explain.

    The grasses living in the cooler region would be expected to have more unsaturated fatty acids in their membranes because those fatty acids remain fluid at lower temperatures. The grasses living immediately adjacent to the hot springs would be expected to have more saturated fatty acids, which would allow the fatty acids to “stack” more closely, making the membranes less fluid and therefore helping them to stay intact at higher temperatures. (Cholesterol could not moderate the effects of temperature on membrane fluidity in this case because it is not found in appreciable quantities in plant cell membranes.)

4.2 5.2 Membrane structure and permeability

  • Selectively permeable: allows some substances to cross more easily than others
    • Nonpolar molecules (hydrophobic) can dissolve in the lipid bilayer and cross it easily
    • Ions and polar molecules (hydrophilic) are impeded by the hydrophobic interior of the membrane, do not cross very rapidly
    • Membrane proteins play key roles in regulating transport

4.2.0.1 Transport proteins:

  • Allow hydrophilic substances to avoid contact with the lipid bilayer
  • Channel proteins: provide a hydrophilic channel for certain molecules or ions to pass through
    • Aquaporins: channel protein that facilitates the passage of water molecules
  • Carrier proteins: hold onto their passengers and change shape in a way that shuttles them across the membrane
  • A transport protein is specific to the substance it moves

4.2.0.2 Concept check

Concept check

  1. Two molecules that can cross a lipid bilayer without help from membrane proteins are O2 and CO2. What property allows this to occur?

    O2 and CO2 are both small, nonpolar molecules that can easily pass through the hydrophobic interior of a membrane.

  2. Why is a transport protein needed to move water molecules rapidly and in large quantities across a membrane?

    Water is a polar molecule, so it cannot pass very rapidly through the hydrophobic region in the middle of a phospholipid bilayer.

  3. Aquaporins exclude passage of hydronium ions (H3O+). Recent research on fat metabolism has shown that some aquaporins allow passage of glycerol, a three-carbon alcohol, as well as H2O. Since H3O+ is much closer in size to water than is glycerol, what do you suppose is the basis of this selectivity?

    The hydronium ion is charged, while glycerol is not. Charge is probably more significant than size as a basis for exclusion by the aquaporin channel.

4.3 5.3 Passive transport

  • Diffusion of a substance across a membrane with no energy investment

  • Diffusion: the movement of a particles so that they tend to spread out evenly into the available space

    • Results in dynamic equilibrium. Molecules continue to cross the membrane, but at equal rates in both directions.
    • A substance diffuses from where it is more concentrated to where it is less concentrated (down its concentration gradient)
    • Unaffected by the concentration gradients of other substances
    • No work must be done, concentration gradient represents potential energy and drives diffusion

4.3.0.1 Water balance:

  • Osmosis: diffusion of water across a selectively permeable membrane
    • Some of the water is clustered around hydrophilic solute molecules and unable to cross the membrane
    • Water diffuses from the region of lower solute concentration (higher free water concentration) to that of higher solute concentration (lower free water concentration)
  • Tonicity: the ability of a solution to cause a cell to gain or lose water
    • Depends on the solution’s concentration of solutes that cannot cross the membrane

    • For cells without walls:
      • Isotonic: no net movement of water, volume of cell is stable (iso “same”)
      • Hypertonic: cell will lose water and shrivel (hyper “more” nonpentrating solutes)
      • Hypertonic: water enters the cell faster than it leaves, cell will swell and lyse (hypo “less”)
      • Osmoregulation: the control of solute concentrations and water balance. A cell without rigid walls can tolerate neither excessive uptake nor excessive loss of water.
    • For cells with walls:
      • Hypotonic: cell swells as water enters, inelastic cell wall exerts a back pressure. Cell is turgid and healthy, provides mechanical support.
      • Isotonic: no net tendency for water to enter, cells become flaccid
      • Hypertonic: as cell shrinks, its plasma membrane pulls away from the wall (plasmolysis)

4.3.0.2 Facilitated diffusion:

  • Passive transport aided by proteins
  • Ion channels: channel protein that transports ions
    • Gated channels: open or close in response to a stimulus
  • Carrier proteins may change shape in response to the binding and release of the transported molecule

4.3.0.3 Concept check

Concept check

  1. How do you think a cell performing cellular respiration rids itself of the resulting CO2?

    CO2 is a nonpolar molecule that can diffuse through the plasma membrane. As long as it diffuses away so that the concentration remains low outside the cell, other CO2 molecules will continue to exit the cell in this way.

  2. In the supermarket, produce is often sprayed with water. Explain why this makes vegetables look crisp.

    The water is hypotonic to the plant cells, so the plant cells take up water. Thus, the cells of the vegetable remain turgid, and the vegetable (for example, lettuce or spinach) remains crisp and does not wilt.

  3. If a Paramecium caudatum cell swims from a hypotonic to an isotonic environment, will its contractile vacuole become more active or less? Why?

    The Paramecium caudatum’s contractile vacuole becomes less active. The vacuole pumps out excess water that accumulates in the cell; this accumulation occurs only in a hypotonic environment.

4.4 5.4 Active transport

  • Some transport proteins can move solutes against their concentration gradients
  • Cells must expend energy, usually supplied by ATP
  • Enables a cell to maintain internal concentrations of solutes that differ from concentrations in its environment
  • Sodium-potassium pump:
    • An animal cell has a much higher concentration of potassium ions (K+) and a much lower concentration of sodium ions (Na+)
    • 3 Na+ are moved out for every 2 K+ pumped in
    • Pump oscillates between two shapes:
      • Protein shape in (1) has a high affinity for Na+, shape in (4) has a high affinity for K+
      • ATP powers the shape change by transferring a phosphate group (phosphorylation) (2). Na+ binding stimulates phosphorylation, K+ binding triggers release of the phosphate group.
    NaKpump

    Figure 4.3: NaKpump

4.4.0.1 Ion pumps maintain membrane potential:

  • Cytoplasmic side of the membrane is negative in charge relative to extracellular side
  • Due to an unequal distribution of anions and cations on the two sides
  • Membrane potential favors the passive transport of cations in the cell and anions out of the cell
  • An ion diffuses down its electrochemical gradient:
    • Combination of a chemical force (concentration gradient) and an electric force
  • Electrogenic pump: transport protein that generates a voltage across a membrane
    • Sodium-potassium pump is the major electrogenic pump fro animal cells (net transfer of one positive charge out of the cell)
    • Proton pumps in plants, fungi, and bacteria actively transport H+ out of the cell
    • Helps store energy that can be tapped for work

4.4.0.2 Cotransport:

  • An ATP-powered pump can indirectly drive the active transport of other solutes:
    • A substance pumped across a membrane can do work as it moves back by diffusion
    • A cotransporter uses this to transport a second substance against its concentration gradient
  • In plants, the H+ gradient stores potential energy that can be used for active transport
    • Return of H+ coupled with the transport of sucrose
Cotransport

Figure 4.4: Cotransport

4.4.0.3 Concept check

Concept check

  1. Sodium-potassium pumps help nerve cells establish a voltage across their plasma membranes. Do these pumps use ATP or produce ATP? Explain.

    The pump uses ATP. To establish a voltage, ions have to be pumped against their gradients, which requires energy.

  2. Explain why the sodium-potassium pump would not be considered a cotransporter.

    Each ion is being transported against its electrochemical gradient. If either ion were transported down its electrochemical gradient, this process would be considered cotransport

  3. Given the internal environment of a lysosome, what transport protein might you expect to see in its membrane?

    The internal environment of a lysosome is acidic, so it has a higher concentration of H+ than does the cytosol. Therefore, you might expect the membrane of the lysosome to have a proton pump to pump H+ into the lysosome.

4.5 5.5 Bulk transport

  • Large molecules cross the membrane by mechanisms that involve packaging in vesicles
  • Requires energy

4.5.0.1 Exocytosis:

  • Cells secrete biological molecules by the fusion of vesicles with the plasma membrane
    • Contents of the vesicle spill out, vesicle membrane becomes part of plasma membrane
  • Used by many secretory cells

4.5.0.2 Endocytosis:

  • Cells take in molecules by forming vesicles from the plasma membrane
    • Small area of the plasma membrane sinks inward to form a pocket
    • As the pocket deepens, it pinches in and forms a vesicles
  • Events look like the reverse of exocytosis

  • Three types:

    • Phagocytosis: cell engulfs a particle by wrapping pseudopodia around it, “cellular eating”
    • Pinocytosis: cell continually gulps droplets of extracellular fluid, “cellular drinking”
      • Nonspecific for the substances it transports
      • Plasma membrane is coated on the cytoplasmic side with a fuzzy layer of proteins
    • Receptor-mediated endocytosis: specialized pinocytosis, specific solutes bind to embedded receptor sites
      • Relatively more bound molecules, but other molecules are also present
      • Receptor proteins are recycled to the plasma membrane by the same vesicle

4.5.0.3 Concept check

Concept check

  1. As a cell grows, its plasma membrane expands. Does this involve endocytosis or exocytosis? Explain.

    Exocytosis. When a transport vesicle fuses with the plasma membrane, the vesicle membrane becomes part of the plasma membrane.

  2. Return to Figure, and circle a patch of plasma membrane that is coming from a vesicle involved in exocytosis.
  3. Describe the cellular pathway of synthesis and deposition of an ECM glycoprotein.

    The glycoprotein would be synthesized in the ER lumen, move through the Golgi apparatus, and then travel in a vesicle to the plasma membrane, where it would undergo exocytosis and become part of the ECM.

4.6 5.6 Cell signaling

4.6.0.1 Local and long-distance signaling:

  • Chemical messages sent out from cells are targeted to other cells that may not be immediately adjacent
  • Cells may communicate through direct contact:
    • Cell junctions that directly connect the cytoplasms of adjacent cells
    • Direct contact between membrane-bound cell-surface molecules in cell-cell recognition
  • In other cases, signaling cells secrete messenger molecules:
    • Local regulators travel only short distances (a, b)
    • Hormones are used for long-distance signaling (c)
    Signaling

    Figure 4.5: Signaling

    1. Paracrine signaling: a secreting cell acts on nearby target cells by discharging local regulators into the extracellular fluid
    2. Synaptic signaling: a nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. More specialized type of local signaling.
    3. Endocrine (hormonal) signaling: specialized endocrine cells secrete hormones into body fluids. Hormones reach all body cells, but are bound only by target cells.

4.6.0.2 The three stages of cell signaling:

  1. Reception: target cell’s detection of a signaling molecule
    • Signaling molecule binds to a receptor protein located at the cell’s surface or inside the cell
  2. Transduction: steps that convert the signal to a form that can bring about a specific cellular response
    • Signal transduction pathway: a sequence of changes in a series of different relay molecules
  3. Transduced signal triggers a response

4.6.0.3 Reception:

  • Signaling molecule behaves as a ligand, a molecule that specifically binds to another molecule
    • Ligand binding causes a receptor protein to undergo a change in shape, directly activating the receptor
    • Most signal receptors are plasma membrane proteins with water-soluble ligands †Receptor tyrosine kinases are discussed in the unabridged textbook and in class, may appear on the AP test
  • G protein-coupled receptor (GPCR):
    • G protein: binds the energy-rich molecule GTP
    1. Signaling molecule binds to the extracellular side of the receptor. Activated receptor binds and activates a G protein.
    2. Activated G protein (carrying GTP) leaves the receptor and binds to an enzyme, altering its shape. Activated enzyme triggers the next step leading to a cellular response.
    • Binding and changes in shape are temporary, molecules soon become available for reuse
      • G protein hydrolyzes GTP to GDP and a phosphate ion
      • Inactive G protein leaves the enzyme, which returns to its original state
    • Many signaling molecules use GPCRs, all GPCRs are remarkably similar in structure

  • Ligand-gated ion channel: membrane receptor with a region that acts as a gate when a certain shape is assumed

    • Gate opens or closes when a signaling molecule binds as a ligand on the extracellular side
    • Allows or blocks the diffusion of specific ions through a channel in the protein
    • Important in the nervous system, neurotransmitter molecules released at a synapse bind to ion channels on the receiving cell
  • Intracellular receptors:
    • Found in either the cytoplasm or nucleus of target cells
    • Signaling molecule must be hydrophobic enough to cross the membrane
    • Testosterone: representative of steroid hormones
      • Secreted by the testes and travels through the blood, entering cells all over the body. Only cells with receptors for testosterone respond
      • Hormone-receptor complex enters the nucleus and turns on specific genes
      • Receptor itself carries out the complete transduction of the signal

4.6.0.4 Transduction:

  • Usually a multistep pathway, provides more coordination and the possibility of greatly amplifying a signal
  • Signal-activated receptor activates another molecule, which activates another molecule, and so on
  • Continues until the protein that produces the final cellular response is activated
  • Original signaling molecule is not passed along. The signal is transduced into different forms, commonly via a shape change in a protein.

  • Protein phosphorylation:

    • Protein kinase: enzyme that transfers phosphate groups from ATP to a protein. Many relay molecules are protein kinases.
    • Phosphorylation cascade: a series of molecules in a pathway are phosphorylated in turn
    • Protein phosphatase: enzyme that removes phosphate groups, dephosphorylation
      • Turns off signal transduction pathway when the initial signal is no longer present
      • Make protein kinases available for reuse
    • Phosphorylation-dephosphorylation acts as a molecular switch, turning an activity on or off as required
  • Small molecules and ions as second messengers:
    • Small, nonprotein, and water-soluble, can spread readily throught the cell by diffusion
    • Two most common second messengers are cyclic AMP (cAMP) and Ca2+
    • G protein signaling pathway with cAMP:
      • First messenger (signaling molecule) activates a GPCR
      • G protein activates adenlyl cyclase, which catalyzes the conversion of ATP to cAMP
      • cAMP activates another protein, usually protein kinase A, leading to cellular responses

4.6.0.5 Response:

  • Regulation of one or more cellular activities
  • Final activated molecule may function as a transcription factor, ultimately regulating protein synthesis
  • Pathway may regulate the activity of a protein (epinephrine activates enzymes that catalyze the breakdown of glycogen)

4.6.0.6 Concept check

Concept check

  1. Explain how nerve cells provide examples of both local and long-distance signaling.

    The secretion of neurotransmitter molecules at a synapse is an example of local signaling. The electrical signal that travels along a very long nerve cell and is passed to the next nerve cell can be considered an example of long-distance signaling. (Note, however, that local signaling at the synapse between two cells is necessary for the signal to pass from one cell to the next.)

  2. When a signal transduction pathway involves a phosphorylation cascade, what turns off the cell’s response?

    Protein phosphatases reverse the effects of the kinases.

  3. How can a target cell’s response to a single hormone molecule result in a response that affects a million other molecules?

    At each step in a cascade of sequential activations, one molecule or ion may activate numerous molecules functioning in the next step.

4.7 Test your understanding

Test your understanding

  1. In what way do the membranes of a eukaryotic cell vary?
    1. Phospholipids are found only in certain membranes. ✗
    2. Certain proteins are unique to each kind of membrane. ✓
    3. Only certain membranes of the cell are selectively permeable. ✗
    4. Only certain membranes are constructed from amphipathic molecules. ✗
    5. Some membranes have hydrophobic surfaces exposed to the cytoplasm, while others have hydrophilic surfaces facing the cytoplasm. ✗
  2. Which of the following factors would tend to increase membrane fluidity?
    1. a greater proportion of unsaturated phospholipids ✓
    2. a greater proportion of saturated phospholipids ✗
    3. a lower temperature ✗
    4. a relatively high protein content in the membrane ✗
    5. a greater proportion of relatively large glycolipids compared with lipids having smaller molecular masses ✗
  3. Phosphorylation cascades involving a series of protein kinases are useful for cellular signal transduction because
    1. they are species specific. ✗
    2. they always lead to the same cellular response. ✗
    3. they amplify the original signal manyfold. ✓
    4. they counter the harmful effects of phosphatases. ✗
    5. the number of molecules used is small and fixed. ✗
  4. Lipid-soluble signaling molecules, such as testosterone, cross the membranes of all cells but affect only target cells because
    1. only target cells retain the appropriate DNA segments. ✗
    2. intracellular receptors are present only in target cells. ✓
    3. most cells lack the Y chromosome required. ✗
    4. only target cells possess the cytosolic enzymes that transduce the testosterone. ✗
    5. only in target cells is testosterone able to initiate a phosphorylation cascade. ✗
  5. Which of the following processes includes all the others?
    1. osmosis ✗
    2. diffusion of a solute across a membrane ✗
    3. facilitated diffusion ✗
    4. passive transport ✓
    5. transport of an ion down its electrochemical gradient ✗
  6. Based on Figure, which of these experimental treatments would increase the rate of sucrose transport into the cell?
    1. decreasing extracellular sucrose concentration ✗
    2. decreasing extracellular pH ✓
    3. decreasing cytoplasmic pH ✗
    4. adding an inhibitor that blocks regeneration of ATP ✗
    5. adding a substance that makes the membrane more permeable to hydrogen ions ✗