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Chapter 7: Cell-Cell Interactions

Chapter Outline

Chapter 7: Cell-Cell Interactions

7.0 Introduction

  1. Cells of Multicellular Organisms Touch and Communicate With Each Other fig 7.1

    2.
    1. Send and Receive Chemical Signals

    2. Coordinate Activities to Behave as Group, Not Individuals

7.1 Cells signal one another with chemicals

  1. Receptor Proteins and Signaling Between Cells

    1. Cellular Communication Is Common in Nature

      1. Occurs in all multicellular organisms

      2. Use a variety of molecules

        1. Some are attached to cell surface

        2. Some are released from cell

    2. Cell Surface Receptors

      1. Cell responds to certain signals, ignores the rest fig 7.2

      2. Feat accomplished by receptor proteins

        1. Have three dimensional shape

        2. Signal molecule binds to receptor if correct shape

        3. Induces shape change in receptor protein

        4. Results in response by cell

    3. The Hunt for Receptor Proteins

      1. Characterizing small number of receptor proteins difficult

      2. Recent techniques have fostered recent advances

        1. Monoclonal antibodies: Used to bind to particular receptors

        2. Gene isolation: Genetic engineering identifies and sequences receptor genes

  2. Types of Cell Signaling

    1. Cells Communicate Through Four Basic Mechanisms fig 7.3

      1. Associated with distance between cells

      2. Some cells send signals to selves

        1. Called autocrine signaling

        2. Plays important role in reinforcing developmental changes

    2. Direct Contact

      1. Cells are very close

      2. Molecules of plasma membrane bind in specific ways

      3. Example: Cell interaction in early development fig 7.3a

    3. Paracrine Signaling

      1. Molecules released by cells and taken up by neighboring cells

      2. Paracrine signals are short-lived with local effects fig 7.3b

      3. Plays important role in early development

    4. Endocrine Signaling

      1. Released signal molecule collected and distributed via blood stream

      2. Molecules called hormones, signaling is endocrine fig 7.3a

      3. Used by plants and animals

    5. Synaptic Signaling

      1. Nervous systems neurons produce neurotransmitters

      2. Released from neurons close to the target cells, persist briefly fig 7.3d

      3. Site of release called chemical synapse

        4.
7.2 Proteins on the cell surface receive signals from other cells

  1. Intracellular Receptors

    1. Common Elements of Cell Signaling Pathways

      1. Intracellular receptors pass through target cell plasma membrane

      2. Nature of receptors that receive the signal tbl 7.1

      3. Function of intracellular receptors fig 7.4

        1. Lipid-soluble or small molecules pass directly across membrane

        2. Bind to receptors in cytoplasm or nucleus

        3. Trigger a variety of responses

    2. Receptors that Act as Gene Regulators

      1. Include similarly structured steroid hormone receptors

      2. Genes may be evolved from single ancestral gene

      3. Grouped in intracellular receptor superfamily

      4. Each receptor has DNA binding site occupied by inhibitory protein fig 7.5

        1. Signal molecule binding to another site on receptor releases inhibitor

        2. Receptor binds then to DNA to activate or suppress gene

      5. Lipid-soluble signals last longer in blood than water-soluble ones

      6. Target cell's response can vary enormously

        1. Binding site on target DNA differs from cell to cell affecting different genes

        2. Most eukaryotic genes have complex controls

    3. Receptors that Act as Enzymes

      1. Example: Nitrous oxide (NO) gas

      2. Binds to guanylyl cyclase in neighboring cells

      3. Activated enzyme catalyzes synthesis of cyclic GMP

      4. Recently recognized as signal molecule in vertebrates

        1. NO initiated response relaxes smooth muscle surrounding blood vessels

        2. Blood vessels expand, increasing blood flow

  2. Cell Surface Receptors

    1. Most Signal Molecules Are Water-Soluble

      1. Cell surface receptors cannot diffuse through cell membranes fig 7.6

      2. Signals bind to receptor proteins on cell surface

      3. Convert extracellular signal to intracellular signal

      4. Produces change in cell's cytoplasm

      5. Include three superfamilies

    2. Chemically Gated Ion Channels

      1. Receptor is multi-pass transmembrane protein fig 7.6a

      2. Winds across plasma membrane several times

      3. Center of protein forms a pore through which ions can pass

      4. Ion channel opens or closes when neurotransmitter binds to protein

        1. Called chemical gating

        2. Type of ion determined by three dimensional shape of ion channel

    3. Enzymatic Receptors

      1. Acts as or are directly linked to enzymes fig 7.6b

      2. Binding between signal molecule and receptor activates the enzyme

      3. Most are protein kinases, add phosphate groups to proteins

      4. Single pass transmembrane protein

        1. Signal molecule binds outside cell

        2. Portion initiating enzyme activity is in cell's cytoplasm

    4. G Protein-Linked Receptors

      1. GTP binding G protein assists membrane-bound enzymes or ion channels fig 7.6c

      2. Discovery of G proteins

        1. Theorized by Rodbell, isolated and purified by Gilman

        2. Involved in mechanism of half of medicines currently in use

        3. Further investigation should show how cells communicate in general

      3. Largest family of cell surface receptors

        1. More than 100 identified

        2. All have similar structure, may be derived from same ancestral sequence

        3. All composed of seven-pass transmembrane protein fig 7.6d

      4. Evolutionary origin of G protein-linked receptors

        1. Same seven-pass structure in a variety of systems

        2. Light-activated bacteriorhodopsin proton pump of bacterial photosynthesis

        3. Yeast mating factor protein recognition receptor

        4. Various sensory receptors including vertebrate rhodopsin

      5. How G protein-linked receptors work

        1. G proteins are mediators that initiate cytoplasmic signal

        2. Link cell surface receptor and cytoplasmic signal pathways

        3. Signal binding causes G protein to bind GTP and become activated

        4. Activated protein diffuses away from receptor to begin actions

        5. Initiates chain of events that results in cell response

7.3 Follow the journey of information into the cell

  1. Initiating the Intracellular Signal

    1. Second Messengers Relay Message

      1. Also called intracellular mediators

      2. Small molecules or ions that change shape and behavior of receptor proteins

      3. Include cyclic adenosine monophosphate (cAMP) and calcium

    2. cAMP

      1. Used as second messenger by all known animal cells fig 7.8

      2. Example: Epinephrine binding to G protein-linked á-adrenergic receptor

        1. Binding epinephrine activates G protein

        2. Enzyme adenylyl cyclase produces large amounts of cAMP in target cell fig 7.9a

          1. cAMP binds to A-kinase

          2. In muscle cells, activates it to phosphorylate cell proteins

        3. Action dependent on cell type, in muscle stimulates glycogen to glucose

    3. Calcium

      1. Ca++ levels in cytoplasm low, high outside cell and in ER

      2. Chemically-gated calcium channels in ER membrane act as switches

        1. Influx of Ca++ from inside ER to cytoplasm triggers many activities

        2. Skeletal muscles contract, some endocrine cells release hormones

        3. Receptor activates G protein which activates phospholipase C enzyme

        4. Phospholipase C catalyzes production of inositol triphosphate (IP3)

        5. IP3 binds to Ca++ channels opening them fig 7.9b

      3. Also initiates response by binding to calmodulin fig 7.10

  2. Amplifying the Signal: Protein Kinase Cascades

    1. Receptors at Surface Receive Signal, But Response Is Elsewhere

      1. Second messengers relay signal to enzymes or genes

      2. Most receptors use other protein messengers to amplify signal to nucleus

    2. Mechanism of the Amplification Process

      1. Receptor phosphorylates stage-one protein

      2. These in turn activate stage-two, then stage-three proteins fig 7.11

      3. Signal amplified since one signal at each step initiates multiple proteins

    3. The Vision Amplification Cascade

      1. Single light-activated rhodopsin activates many transducin molecules

      2. Each transducin causes modification of cyclic GMP fig 7.12

      3. One rhodopsin ultimately causes split of 105 cyclic GMP's fig 7.13

    4. The Cell Division Amplification Cascade

      1. Cell division controlled by receptor that acts as a protein kinase

      2. Receptor phosphorylates ras protein

      3. Ras in turn activates multiple phosphorylation cascades

      4. Hyperactive ras (as in cancer) results in uncontrolled cell division

7.4 Cell surface proteins mediate cell-cell interactions

  1. The Expression of Cell Identity

    1. Tissues Are a Fundamental Property of Multicellular Organisms

      1. All cells within a tissue are identified as members of that tissue

      2. Identification results from the presence of unique cell surface markers

    2. Tissue-Specific Identity Markers

      1. Glycolipids

        1. Lipids with carbohydrate heads fig 7.14

        2. Markers on surface of red blood cells identify A, B, O blood types

        3. Cell populations of glycolipids change as cells differentiate

      2. MHC Proteins

        1. Immune system cell surface markers distinguish between "self" and "not self"

        2. Immune system "self" marker proteins

        3. Major histocompatibility complex proteins

        4. Single pass proteins anchored in the plasma membrane

        5. Many are members of immunoglobulin receptor superfamily fig 7.15

        6. Immune system cells inspect other cells, destroy ones with "not self" markers

  2. Intercellular Adhesion

    1. Cell Junctions Are Long-Lasting Physical Connections Between Cells fig 7.16

      1. Nature of the connection determines what tissue is like

      2. Tissue function dependent on how individual cells arranged within it

      3. Divided into three categories fig 7.17

    2. Tight Junctions

      1. Connect adjacent cells to prevent small molecules from leaking fig 7.18

        1. Cells act as wall within an organ

        2. Molecules sequestered within a region

      2. Creating sheets of cells

        1. Cells lining digestive tract only one cell layer thick

        2. One surface faces inside, other surface faces extracellular space with blood vessels

        3. Tight junctions encircle each cell in sheet like belt

        4. Ensure that materials pass through cells, not between cells

      3. Partitioning the sheet

        1. Partition plasma membranes of lining cells into separate compartments

        2. Nutrient transport proteins must stay in proper orientation to function

        3. Segregate different proteins on opposite sides of sheet, can't drift between

    3. Anchoring Junctions

      1. Attach cell's cytoskeleton to that of other cells or extracellular matrix

      2. Common in sheets of tissues exposed to stress like muscle, skin epithelium

      3. Cadherin-mediated links

        1. Desmosomes connect cytoskeletons of adjacent cells fig 7.19

        2. Hemidesmosomes anchor epithelial cells to basement membrane

        3. Cadherin single-pass transmembrane glycoproteins create critical link

          1. Cytoplasmic end linked to intermediate filaments

          2. Other end projects through membrane links to cadherin of next cell

        4. More secure than connection to free-floating membrane proteins

        5. Cadherins also connect to cell's actin framework, less stable connection fig 7.20

          1. Migration of neurons in development

          2. May provide "roadmap" for cells to find their destination

      4. Integrin-mediated links

        1. Adherens junctions fig 7.21

          1. One side connect actin filament of a cell

          2. Other side linked to neighbor cell or extracellular matrix

        2. Linking proteins belong to superfamily of receptors called integrins

        3. Integrin is transmembrane protein made of two glycoprotein subunits

        4. Component of matrix that cell bind to depends on integrin combination

  3. Communicating Between Cells

    1. Communicating Junctions

      1. Some cells communicate through direct connections between cells

      2. Pass chemical signals from one cell to another

      3. Permit small molecules or ions to pass from cell to cell

    2. Gap Junctions In Animals fig 7.22

      1. Composed of connexons

        1. Six identical transmembrane proteins arranged in a circle

        2. Connexons of two adjacent cells must be perfectly aligned

        3. Small molecules like sugars and amino acids can pass

      2. Are dynamic structures that can open and close

        1. Respond to factors like Ca++ and H+ ions

        2. If cell damaged ions flow in, close gap junctions, seal off cell

    3. Plasmodesmata in Plants fig 7.23

      1. Occur only at gaps in cell walls, provide cytoplasmic connections between cells

      2. Function like animal cell gap junctions

      3. Are lined with plasma membrane

      4. Contain central tubule connecting ER of both cells

      5. Play role in integrating activities of plant body

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