Cell-Matrix Junctions and Integrin Function 4
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Cell-Matrix Junctions and Integrin Function 4

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Questions and Answers

What is the primary role of integrins in cells?

  • Regulating gene expression
  • Degrading extracellular matrix components
  • Transporting nutrients across the cell membrane
  • Transmitting signals between the extracellular matrix and cytoskeleton (correct)

    • Matrix receptors have no influence on a cell's behavior.

    False

    What are the two subunits that compose an integrin molecule?

    α and β

    The principal receptors for binding most extracellular matrix proteins in animal cells are called ______.

    <p>integrins</p> Signup and view all the answers

    Match the following components with their functions:

    <p>Integrins = Link extracellular matrix to cytoskeleton Cadherins = Cell-cell adhesion Transmembrane proteoglycans = Act as co-receptors Basal lamina = Support for epithelial cells</p> Signup and view all the answers

    What can cause an integrin to tighten its grip on structures?

    <p>Mechanical tension applied to the integrin</p> Signup and view all the answers

    Integrins can only transmit signals from the extracellular matrix to the cell interior.

    <p>False</p> Signup and view all the answers

    What type of molecules can function as matrix receptors or co-receptors?

    <p>Transmembrane proteoglycans</p> Signup and view all the answers

    What is the best-understood binding site for integrins?

    <p>RGD sequence</p> Signup and view all the answers

    Humans possess 24 types of integrins formed from the products of 8 different β-chain genes and 18 different α-chain genes.

    <p>True</p> Signup and view all the answers

    Name the giant protein that acts as an adaptor for integrins.

    <p>talin</p> Signup and view all the answers

    The intracellular portion of an integrin dimer binds to a complex of several different __________.

    <p>proteins</p> Signup and view all the answers

    Which integrin is responsible for linking epithelium to basal lamina?

    <p>α6β4 integrin</p> Signup and view all the answers

    Integrins are only involved in cell-matrix interactions.

    <p>False</p> Signup and view all the answers

    What condition can arise from defects in integrins?

    <p>blistering disease</p> Signup and view all the answers

    Which integrin subunit forms dimers with at least four types of alpha subunits and is exclusively found on white blood cells?

    <p>β2 subunit</p> Signup and view all the answers

    The binding of integrins is influenced by the concentration of __________ in the extracellular medium.

    <p>Ca2+ and Mg2+</p> Signup and view all the answers

    Individuals with the genetic disease leukocyte adhesion deficiency can synthesize functional β2 subunits.

    <p>False</p> Signup and view all the answers

    Match the following integrins with their respective ligands:

    <p>α5β1 = Fibronectin α6β1 = Laminin αLβ2 = ICAM1 αIIbβ3 = Fibrinogen</p> Signup and view all the answers

    What is the primary role of β3 integrins found on blood platelets?

    <p>To mediate normal blood clotting by binding to matrix proteins like fibrinogen.</p> Signup and view all the answers

    The process by which a cell can switch its attachment to the extracellular matrix is called _____ of integrins.

    <p>activation</p> Signup and view all the answers

    What occurs if a single β1 subunit is mutated?

    <p>Immediate embryonic death</p> Signup and view all the answers

    Match the following integrin subunits with their associated functions:

    <p>α7 = Muscle attachment β2 = White blood cell functionality β3 = Blood clotting αLβ2 = Cell adhesion at sites of infection</p> Signup and view all the answers

    A specific type of integrin anchors keratin filaments to the extracellular matrix.

    <p>True</p> Signup and view all the answers

    What is one mechanism by which integrins switch from an inactive to an active state?

    <p>Outside-in mechanism through binding of matrix proteins</p> Signup and view all the answers

    What kind of junctions do integrins help form in epithelial cells?

    <p>hemidesmosomes</p> Signup and view all the answers

    The β3 integrin is primarily responsible for cell-cell interactions in white blood cells.

    <p>False</p> Signup and view all the answers

    The ________________ disease can result from an autoimmune response against collagen XVII or BP230.

    <p>bullous pemphigoid</p> Signup and view all the answers

    Which integrin is associated with leukocyte adhesion?

    <p>αLβ2</p> Signup and view all the answers

    What happens when talin binds to the β chain of an integrin?

    <p>It blocks the intracellular α–β linkage, allowing the integrin to activate.</p> Signup and view all the answers

    Integrin linkages depend solely on talin for proper function.

    <p>False</p> Signup and view all the answers

    Integrins switch conformations between _____ and _____ states based on external and internal signals.

    <p>active, inactive</p> Signup and view all the answers

    Match the following diseases with their associated integrin deficiencies:

    <p>Muscular dystrophy = α7 subunit deficiency Leukocyte adhesion deficiency = β2 subunit deficiency Glanzmann disease = β3 integrin deficiency</p> Signup and view all the answers

    What is one role of integrins in relation to cytoskeletal attachments?

    <p>They facilitate the attachment of actin filaments to the intracellular end of the integrin.</p> Signup and view all the answers

    Cellular movement requires both the making and breaking of attachments mediated by integrins.

    <p>True</p> Signup and view all the answers

    What is the significance of the Ig superfamily of cell-adhesion molecules in integrin function?

    <p>They serve as ligands for integrins, allowing cell-cell adhesion.</p> Signup and view all the answers

    The binding protein that helps in the activation of integrins in platelets is called _____ .

    <p>thrombin</p> Signup and view all the answers

    What protein does activated Rap1 interact with to facilitate the recruitment of talin?

    <p>RIAM</p> Signup and view all the answers

    Talin interacts with actin and adaptor proteins only after being recruited by RIAM to the plasma membrane.

    <p>True</p> Signup and view all the answers

    What is the role of integrins in cell attachment?

    <p>Integrins bind to the extracellular matrix and facilitate cell adhesion.</p> Signup and view all the answers

    Talin unfolds to expose its binding sites for ______ and ______ upon recruitment.

    <p>integrin, actin</p> Signup and view all the answers

    Which of the following proteins is NOT mentioned as part of cell-matrix junctions?

    <p>Myosin</p> Signup and view all the answers

    Integrins bind ligands with high affinity and low concentration on the cell surface.

    <p>False</p> Signup and view all the answers

    Which complex serves as an organizing hub at many junctions involving integrins?

    <p>ILK complex (integrin-linked kinase, pinch, parvin)</p> Signup and view all the answers

    Anchorage dependence is primarily mediated by ______ and the intracellular signals they generate.

    <p>integrins</p> Signup and view all the answers

    Which of the following describes the function of focal adhesion kinase (FAK)?

    <p>It serves as a signaling hub regulating cell behavior.</p> Signup and view all the answers

    Match the following proteins with their roles in cell adhesion:

    <p>Talin = Unfolds to expose binding sites Vinculin = Binds to actin filaments Kindlin = Works with talin in integrin activation FAK = Involved in intracellular signaling</p> Signup and view all the answers

    Cells can grow and proliferate in culture without being attached to the extracellular matrix.

    <p>False</p> Signup and view all the answers

    What happens to epithelial, endothelial, and muscle cells when they lose contact with the extracellular matrix?

    <p>They undergo apoptosis.</p> Signup and view all the answers

    The clustered FAK molecules phosphorylate each other on a specific ______, creating a docking site for signaling proteins.

    <p>tyrosine</p> Signup and view all the answers

    What is the role of kindlin in integrin activation?

    <p>Interacts with talin</p> Signup and view all the answers

    Describe the Velcro principle in the context of integrin adhesion.

    <p>Integrins cluster together to create a dense plaque, enhancing adhesion strength.</p> Signup and view all the answers

    What role do integrins play in cells?

    <p>They act as cell-surface receptors for extracellular matrix</p> Signup and view all the answers

    Cell–matrix junctions do not respond to mechanical forces.

    <p>False</p> Signup and view all the answers

    What are the two types of filaments integrins primarily connect to in cells?

    <p>Actin filaments and intermediate filaments.</p> Signup and view all the answers

    Integrins are ________, which means they are composed of two different subunits.

    <p>heterodimers</p> Signup and view all the answers

    Match the following terms to their correct definitions:

    <p>Integrin = Principal cell-surface receptor for ECM binding Talin = Links integrins to actin Vinculin = Aids in strengthening junction attachments Mechanotransduction = The process of cells sensing mechanical forces</p> Signup and view all the answers

    What happens to the vinculin-binding sites in talin when it is stretched?

    <p>They are exposed and can bind to vinculin</p> Signup and view all the answers

    Anchorage dependence refers to the need for cells to be attached to a surface for growth and survival.

    <p>True</p> Signup and view all the answers

    Which protein is primarily responsible for the conformational switch of integrins from inactive to active?

    <p>Talin</p> Signup and view all the answers

    The ________ filaments in cell–matrix junctions provide contractile forces that affect junction stability.

    <p>actin</p> Signup and view all the answers

    What effect does attaching to a rigid matrix have on cell–matrix junctions?

    <p>Increases tension and strength of the junction</p> Signup and view all the answers

    Signals from integrins only act in one direction, either outside-in or inside-out.

    <p>False</p> Signup and view all the answers

    What type of adhesion sites concentrate proteins containing phosphotyrosine?

    <p>Focal adhesions</p> Signup and view all the answers

    The process whereby cells respond to differences in the rigidity of the extracellular matrix is known as _________.

    <p>mechanotransduction</p> Signup and view all the answers

    Match the following functions to their respective proteins:

    <p>Talin = Adaptor linking integrins to actin Vinculin = Recruits additional actin filaments FAK = Facilitates signaling at adhesion sites Integrins = Connect extracellular matrix to the cytoskeleton</p> Signup and view all the answers

    Study Notes

    Cell-Matrix Junctions

    • Cells interact with the extracellular matrix through transmembrane cell adhesion proteins that act as matrix receptors.
    • These proteins bind to the matrix outside the cell and the cytoskeleton inside the cell.
    • Integrins are the principal receptors for binding most extracellular matrix proteins.
    • Integrins are transmembrane heterodimers, consisting of two subunits, alpha (α) and beta (β).
    • Both subunits span the cell membrane and have extracellular domains that bind to specific sequences in extracellular matrix proteins.
    • Integrins can transmit signals in both directions across the plasma membrane.
    • Binding of a matrix component to an integrin can send a signal into the cell, and conditions in the cell interior can send a signal outward to control binding of the integrin to the matrix.

    Integrin Structure and Function

    • The extracellular domains of integrins bind to specific amino acid sequences in extracellular matrix proteins.
    • The intracellular portion of an integrin dimer binds to a complex of proteins that form a linkage to the cytoskeleton, primarily actin filaments.
    • Talin is a major adaptor protein that links integrins to the cytoskeleton.
    • Hemidesmosomes, a specialized cell-matrix attachment site in epithelial cells, anchor cells to laminin in the basal lamina.
    • Defects in integrins can lead to various genetic diseases, including muscular dystrophy and leukocyte adhesion deficiency.

    Integrin Activation

    • Integrins can switch between an active and inactive conformation.
    • Activation can occur by an "outside-in" mechanism, where binding of an external matrix protein induces a conformational change exposing binding sites for adaptor proteins and enabling linkage to the cytoskeleton.
    • Activation can also occur by an "inside-out" mechanism, where intracellular signals stimulate the ability of adaptor proteins, like talin, to interact with the β chain of the integrin.
    • This conformational change exposes the external and internal ligand-binding sites on the integrin molecule, coupling extracellular matrix binding and intracellular cytoskeleton linkages.

    Integrin Clustering and Cell-Matrix Junction Formation

    • Integrins cluster together to form dense plaques, creating strong adhesions to the extracellular matrix.
    • The assembly of these junctional complexes depends on the recruitment of various scaffolding and signaling proteins, including talin, ILK, and FAK.

    Integrin Signaling and Cell Behavior

    • Integrins activate intracellular signaling pathways, impacting various aspects of cell behavior.
    • Anchorage dependence, referring to the dependence of cell growth, proliferation, and survival on attachment to a substratum, is mainly mediated by integrins and the intracellular signals they generate.
    • Integrins recruit intracellular signaling proteins, such as FAK, promoting cell survival and proliferation.
    • The Ras-MAP kinase pathway can be activated by both integrins and conventional signaling receptors.

    Focal Adhesion Kinase (FAK)

    • FAK is a cytoplasmic protein tyrosine kinase recruited to integrin β subunits at sites of cell-matrix contact.
    • It plays a crucial role in integrin signaling, phosphorylating itself and recruiting other signaling proteins, ultimately impacting cell behavior.

    Integrin Signaling

    • Integrins are essential cell-surface receptors mediating cell attachment to the extracellular matrix (ECM).
    • They act as transmembrane linkers connecting the ECM to the cytoskeleton.
    • Most integrins bind to actin filaments, while some at hemidesmosomes bind to intermediate filaments.
    • Integrins are heterodimers composed of α and β subunits.
    • Ligand binding or intracellular activator protein binding (e.g., talin) triggers a conformational switch in integrins, transitioning them from an inactive to an active state.
    • This conformational change establishes an allosteric coupling between ECM binding and cytoskeleton binding, enabling bidirectional signaling across the plasma membrane.
    • Activated integrins organize complex protein assemblies, initiating intracellular signals that influence various cellular processes, including proliferation, survival, polarity, and migration.
    • Anchorage dependence, the reliance of cells on attachment to a substratum for growth and survival, is directly linked to integrin signaling.

    Mechanotransduction at Cell-Matrix Junctions

    • Cell-matrix junctions, like cell-cell junctions, can sense and respond to mechanical forces.
    • They are often linked to contractile actin networks that pull the junctions inward.
    • When cells attach to a rigid matrix, the junction senses high tension, prompting the recruitment of additional integrins and proteins to strengthen the junction.
    • Attachment to a softer matrix generates less tension, resulting in a less robust response.
    • This allows cells to differentiate between ECM rigidity in various tissues and tailor their responses accordingly.

    Talin as a Tension Sensor

    • Talin, a protein connecting integrins to actin filaments, acts as a tension sensor at cell-matrix junctions.
    • It contains numerous binding sites for vinculin, an actin-regulatory protein.
    • These sites are concealed within folded protein domains and exposed when stretching unfolds these domains.
    • The N-terminus of talin binds to integrins, while the C-terminus binds to actin.
    • Myosin-driven pulling of actin filaments stretches the talin rod, exposing vinculin-binding sites.
    • Vinculin then recruits and organizes additional actin filaments, reinforcing the junction and increasing its strength.

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    Description

    This quiz covers the role of integrins as key receptors that mediate interactions between cells and the extracellular matrix. It explores the structure of integrins, their binding mechanisms, and the bidirectional signaling pathways they facilitate. Test your understanding of cell adhesion and matrix receptor dynamics.

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