Cell Membranes and Signaling

Cell Membranes and Signaling
5 Cell Membranes and Signaling

Chapter 5 Cell Membranes and Signaling
Key Concepts 5.1 Biological Membranes Have a Common Structure and Are Fluid 5.2 Some Substances Can Cross the Membrane by Diffusion 5.3 Some Substances Require Energy to Cross the Membrane

Chapter 5 Cell Membranes and Signaling
5.4 Large Molecules Cross the Membrane via Vesicles 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals 5.6 Signal Transduction Allows the Cell to Respond to Its Environment

Concept 5.1 Biological Membranes Have a Common Structure and Are Fluid
A membrane’s structure and functions are determined by its constituents: lipids, proteins, and carbohydrates. The general structure of membranes is known as the fluid mosaic model. Phospholipids form a bilayer which is like a “lake” in which a variety of proteins “float.” VIDEO 5.1 Cell Visualization: Membranes, hormones, and receptors

Figure 5.1 Membrane Molecular Structure

Lipids form the hydrophobic core of the membrane. Most lipid molecules are phospholipids with two regions: Hydrophilic regions—electrically charged “heads” that associate with water molecules Hydrophobic regions—nonpolar fatty acid “tails” that do not dissolve in water

Two important factors in membrane fluidity: Lipid composition—types of fatty acids can increase or decrease fluidity Temperature—membrane fluidity decreases in colder conditions APPLY THE CONCEPT Biological membranes have a common structure and are fluid INTERACTIVE TUTORIAL 5.1 Lipid Bilayer: Temperature Effects on Composition

Biological membranes contain proteins, with varying ratios of phospholipids. Peripheral membrane proteins lack hydrophobic groups and are not embedded in the bilayer. Integral membrane proteins are partly embedded in the phospholipid bilayer. See Figure 5.1

Anchored membrane proteins have lipid components that anchor them in the bilayer. Proteins are asymmetrically distributed on the inner and outer membrane surfaces. A transmembrane protein extends through the bilayer on both sides, and may have different functions in its external and transmembrane domains.

Plasma membrane carbohydrates are located on the outer membrane and can serve as recognition sites. Glycolipid—a carbohydrate bonded to a lipid Glycoprotein—a carbohydrate bonded to a protein

Concept 5.2 Some Substances Can Cross the Membrane by Diffusion
Biological membranes allow some substances, and not others, to pass. This is known as selective permeability. Two processes of transport: Passive transport does not require metabolic energy. Active transport requires input of metabolic energy.

Passive transport of a substance can occur through two types of diffusion: Simple diffusion through the phospholipid bilayer Facilitated diffusion through channel proteins or aided by carrier proteins

Diffusion is the process of random movement toward equilibrium. Speed of diffusion depends on three factors: Diameter of the molecules—smaller molecules diffuse faster Temperature of the solution—higher temperatures lead to faster diffusion

The concentration gradient in the system—the greater the concentration gradient in a system, the faster a substance will diffuse A higher concentration inside the cell causes the solute to diffuse out, and a higher concentration outside causes the solute to diffuse in, for many molecules.

Simple diffusion takes place through the phospholipid bilayer. A molecule that is hydrophobic and soluble in lipids can pass through the membrane. Polar molecules do not pass through— they are not soluble in the hydrophilic interior and form bonds instead in the aqueous environment near the membrane.

Osmosis is the diffusion of water across membranes. It depends on the concentration of solute molecules on either side of the membrane. Water passes through special membrane channels.

When comparing two solutions separated by a membrane: A hypertonic solution has a higher solute concentration. Isotonic solutions have equal solute concentrations. A hypotonic solution has a lower solute concentration.

Figure 5.3A Osmosis Can Modify the Shapes of Cells

Figure 5.3B Osmosis Can Modify the Shapes of Cells

Figure 5.3C Osmosis Can Modify the Shapes of Cells

The concentration of solutes in the environment determines the direction of osmosis in all animal cells. In other organisms, cell walls limit the volume that can be taken up. Turgor pressure is the internal pressure against the cell wall—as it builds up, it prevents more water from entering.

Diffusion may be aided by channel proteins. Channel proteins are integral membrane proteins that form channels across the membrane. Substances can also bind to carrier proteins to speed up diffusion. Both are forms of facilitated diffusion.

Ion channels are a type of channel protein—most are gated, and can be opened or closed to ion passage. A gated channel opens when a stimulus causes the channel to change shape. The stimulus may be a ligand, a chemical signal.

A ligand-gated channel responds to its ligand. A voltage-gated channel opens or closes in response to a change in the voltage across the membrane.

Figure 5.4 A Ligand-Gated Channel Protein Opens in Response to a Stimulus

Water crosses membranes at a faster rate than simple diffusion. It may “hitchhike” with ions such as Na+ as they pass through channels. Aquaporins are specific channels that allow large amounts of water to move along its concentration gradient.

Carrier proteins in the membrane facilitate diffusion by binding substances. Glucose transporters are carrier proteins in mammalian cells. Glucose molecules bind to the carrier protein and cause the protein to change shape—it releases glucose on the other side of the membrane.

Figure 5.6 A Carrier Protein Facilitates Diffusion (Part 1)

Transport by carrier proteins differs from simple diffusion, though both are driven by the concentration gradient. The facilitated diffusion system can become saturated—when all of the carrier molecules are bound, the rate of diffusion reaches its maximum. ANIMATED TUTORIAL 5.1 Passive Transport

Concept 5.3 Some Substances Require Energy to Cross the Membrane
Active transport requires the input of energy to move substances against their concentration gradients. Active transport is used to overcome concentration imbalances that are maintained by proteins in the membrane.

Table 5.1 Membrane Transport Mechanisms

The energy source for active transport is often ATP. Active transport is directional and moves a substance against its concentration gradient. A substance moves in the direction of the cell’s needs, usually by means of a specific carrier protein.

Two types of active transport: Primary active transport involves hydrolysis of ATP for energy. Secondary active transport uses the energy from an ion concentration gradient, or an electrical gradient.

The sodium–potassium (Na+–K+) pump is an integral membrane protein that pumps Na+ out of a cell and K+ in. One molecule of ATP moves two K+ and three Na+ ions.

Figure 5.7 Primary Active Transport: The Sodium–Potassium Pump

Concept 5.4 Large Molecules Cross the Membrane via Vesicles
Macromolecules are too large or too charged to pass through biological membranes and instead pass through vesicles. To take up or to secrete macromolecules, cells must use endocytosis or exocytosis.

Figure 5.8 Endocytosis and Exocytosis (Part 1)

Figure 5.8 Endocytosis and Exocytosis (Part 2)

Three types of endocytosis brings molecules into the cell: phagocytosis, pinocytosis, and receptor–mediated endocytosis. In all three, the membrane invaginates, or folds around the molecules and forms a vesicle. The vesicle then separates from the membrane.

In phagocytosis (“cellular eating”), part of the membrane engulfs a large particle or cell. A food vacuole (phagosome) forms and usually fuses with a lysosome, where contents are digested. LINK Review the discussion of phagocytosis in Concept 4.3

In pinocytosis (“cellular drinking”), vesicles also form. The vesicles are smaller and bring in fluids and dissolved substances, as in the endothelium near blood vessels. VIDEO 5.2 Pinocytosis and membrane ruffling in a mouse epithelial cell

Receptor–mediated endocytosis depends on receptors to bind to specific molecules (their ligands). The receptors are integral membrane proteins located in regions called coated pits. The cytoplasmic surface is coated by another protein (often clathrin).

When receptors bind to their ligands, the coated pit invaginates and forms a coated vesicle. The clathrin stabilizes the vesicle as it carries the macromolecules into the cytoplasm. Once inside, the vesicle loses its clathrin coat and the substance is digested. APPLY THE CONCEPT Some substances require energy to cross the membrane VIDEO 5.3 Cell Visualization: Endocytosis

Figure 5.9 Receptor-Mediated Endocytosis (Part 1)

Figure 5.9 Receptor-Mediated Endocytosis (Part 2)

Exocytosis moves materials out of the cell in vesicles. The vesicle membrane fuses with the plasma membrane and the contents are released into the cellular environment. Exocytosis is important in the secretion of substances made in the cell. ANIMATED TUTORIAL 5.3 Endocytosis and Exocytosis VIDEO 5.4 Exocytosis of coccoliths in a marine golden alga, Pleurochrysis

Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals
Cells can respond to many signals if they have a specific receptor for that signal. A signal transduction pathway is a sequence of molecular events and chemical reactions that lead to a cellular response, following the receptor’s activation by a signal.

Cells are exposed to many signals and may have different responses:
Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Cells are exposed to many signals and may have different responses: Autocrine signals affect the same cells that release them. Paracrine signals diffuse to and affect nearby cells. Hormones travel to distant cells.

Figure 5.10 Chemical Signaling Concepts

Only cells with the necessary receptors can respond to a signal—the target cell must be able to sense it and respond to it. A signal transduction pathway involves a signal, a receptor, and a response.

Figure 5.11 Signal Transduction Concepts

A common mechanism of signal transduction is allosteric regulation.
Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals A common mechanism of signal transduction is allosteric regulation. This involves an alteration in a protein’s shape as a result of a molecule binding to it. A signal transduction pathway may produce short or long term responses. See Figure 5.6

Figure 5.12 A Signal Binds to Its Receptor

An inhibitor, or antagonist, can bind in place of the normal ligand.
Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Ligands are generally not metabolized further, but their binding may expose an active site on the receptor. Binding is reversible and the ligand can be released, to end stimulation. An inhibitor, or antagonist, can bind in place of the normal ligand. See Figure 5.6

Receptors can be classified by their location in the cell.
Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Receptors can be classified by their location in the cell. This is determined by whether or not their ligand can diffuse through the membrane. VIDEO 5.5 Cell Visualization: Signals and calcium

Cytoplasmic receptors have ligands, such as estrogen, that are small or nonpolar and can diffuse across the membrane. Membrane receptors have large or polar ligands, such as insulin, that cannot diffuse and must bind to a transmembrane receptor at an extracellular site.

Receptors are also classified by their activity: Ion channel receptors
Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Receptors are also classified by their activity: Ion channel receptors Protein kinase receptors G protein–linked receptors VIDEO 5.5 Cell Visualization: Signals and calcium

Ion channel receptors, or gated ion channels, change their three- dimensional shape when a ligand binds. The acetylcholine receptor, a ligand- gated sodium channel, binds acetylcholine to open the channel and allow Na+ to diffuse into the cell. See Figure 5.4 LINK Nerve cells communicate with muscle cells at neuromuscular junctions, which are described in Concept 36.1

Protein kinase receptors change their shape when a ligand binds.
Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Protein kinase receptors change their shape when a ligand binds. The new shape exposes or activates a cytoplasmic domain that has catalytic (protein kinase) activity.

Figure 5.13 A Protein Kinase Receptor

Protein kinases catalyze the following reaction:
Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Protein kinases catalyze the following reaction: ATP + protein  ADP + phosphorylated protein Each protein kinase has a specific target protein, whose activity is changed when it is phosphorylated.

Ligands binding to G protein–linked receptors expose a site that can bind to a membrane protein, a G protein. The G protein is partially inserted in the lipid bilayer, and partially exposed on the cytoplasmic surface.

Many G proteins have three subunits and can bind three molecules:
Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Many G proteins have three subunits and can bind three molecules: The receptor GDP and GTP, used for energy transfer An effector protein to cause an effect in the cell

The activated G protein–linked receptor exchanges a GDP nucleotide bound to the G protein for a higher energy GTP. The activated G protein activates the effector protein, leading to signal amplification. ANIMATED TUTORIAL 5.4 G Protein–Linked Signal Transduction and Cancer

Figure 5.14 A G Protein–Linked Receptor

Concept 5.6 Signal Transduction Allows the Cell to Respond to Its Environment
Signal activation of a specific receptor leads to a cellular response, which is mediated by a signal transduction pathway. Signaling can initiate a cascade of protein interactions—the signal can then be amplified and distributed to cause different responses. VIDEO 5.6 Chemotaxis of human neutrophils

A second messenger is an intermediary between the receptor and the cascade of responses. In the fight-or-flight response, epinephrine (adrenaline) activates the liver enzyme glycogen phosphorylase. The enzyme catalyzes the breakdown of glycogen to provide quick energy.

Signal transduction pathways involve multiple steps—enzymes may be either activated or inhibited by other enzymes. In liver cells, a signal cascade begins when epinephrine stimulates a G protein–mediated protein kinase pathway.

Epinephrine binds to its receptor and activates a G protein.
Concept 5.6 Signal Transduction Allows the Cell to Respond to Its Environment Epinephrine binds to its receptor and activates a G protein. cAMP is produced and activates protein kinase A—it phosphorylates two other enzymes, with opposite effects: Inhibition Activation

Figure 5.17 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 1)

Figure 5.17 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 2)

Inhibition—protein kinase A inactivates glycogen synthase through phosphorylation, and prevents glucose storage. Activation—Phosphorylase kinase is activated when phosphorylated and is part of a cascade that results in the liberation of glucose molecules. See Figure 5.17, step 1 See Figure 5.17, steps 2 and 3 ANIMATED TUTORIAL 5.5 Signal Transduction Pathway

Signal transduction ends after the cell responds—enzymes convert each transducer back to its inactive precursor. The balance between the regulating enzymes and the signal enzymes determines the cell’s response.

Cells can alter the balance of enzymes in two ways:
Concept 5.6 Signal Transduction Allows the Cell to Respond to Its Environment Cells can alter the balance of enzymes in two ways: Synthesis or breakdown of the enzyme Activation or inhibition of the enzymes by other molecules

Cell functions change in response to environmental signals:
Concept 5.6 Signal Transduction Allows the Cell to Respond to Its Environment Cell functions change in response to environmental signals: Opening of ion channels Alterations in gene expression Alteration of enzyme activities See Figure 5.4 See Figure 5.17 VIDEO 5.7 Calcium waves in brain glial cells

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