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What is the primary role of integrins in cells?
What is the primary role of integrins in cells?
Matrix receptors have no influence on a cell's behavior.
Matrix receptors have no influence on a cell's behavior.
False
What are the two subunits that compose an integrin molecule?
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 ______.
The principal receptors for binding most extracellular matrix proteins in animal cells are called ______.
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Match the following components with their functions:
Match the following components with their functions:
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What can cause an integrin to tighten its grip on structures?
What can cause an integrin to tighten its grip on structures?
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Integrins can only transmit signals from the extracellular matrix to the cell interior.
Integrins can only transmit signals from the extracellular matrix to the cell interior.
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What type of molecules can function as matrix receptors or co-receptors?
What type of molecules can function as matrix receptors or co-receptors?
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What is the best-understood binding site for integrins?
What is the best-understood binding site for integrins?
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Humans possess 24 types of integrins formed from the products of 8 different β-chain genes and 18 different α-chain genes.
Humans possess 24 types of integrins formed from the products of 8 different β-chain genes and 18 different α-chain genes.
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Name the giant protein that acts as an adaptor for integrins.
Name the giant protein that acts as an adaptor for integrins.
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The intracellular portion of an integrin dimer binds to a complex of several different __________.
The intracellular portion of an integrin dimer binds to a complex of several different __________.
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Which integrin is responsible for linking epithelium to basal lamina?
Which integrin is responsible for linking epithelium to basal lamina?
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Integrins are only involved in cell-matrix interactions.
Integrins are only involved in cell-matrix interactions.
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What condition can arise from defects in integrins?
What condition can arise from defects in integrins?
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Which integrin subunit forms dimers with at least four types of alpha subunits and is exclusively found on white blood cells?
Which integrin subunit forms dimers with at least four types of alpha subunits and is exclusively found on white blood cells?
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The binding of integrins is influenced by the concentration of __________ in the extracellular medium.
The binding of integrins is influenced by the concentration of __________ in the extracellular medium.
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Individuals with the genetic disease leukocyte adhesion deficiency can synthesize functional β2 subunits.
Individuals with the genetic disease leukocyte adhesion deficiency can synthesize functional β2 subunits.
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Match the following integrins with their respective ligands:
Match the following integrins with their respective ligands:
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What is the primary role of β3 integrins found on blood platelets?
What is the primary role of β3 integrins found on blood platelets?
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The process by which a cell can switch its attachment to the extracellular matrix is called _____ of integrins.
The process by which a cell can switch its attachment to the extracellular matrix is called _____ of integrins.
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What occurs if a single β1 subunit is mutated?
What occurs if a single β1 subunit is mutated?
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Match the following integrin subunits with their associated functions:
Match the following integrin subunits with their associated functions:
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A specific type of integrin anchors keratin filaments to the extracellular matrix.
A specific type of integrin anchors keratin filaments to the extracellular matrix.
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What is one mechanism by which integrins switch from an inactive to an active state?
What is one mechanism by which integrins switch from an inactive to an active state?
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What kind of junctions do integrins help form in epithelial cells?
What kind of junctions do integrins help form in epithelial cells?
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The β3 integrin is primarily responsible for cell-cell interactions in white blood cells.
The β3 integrin is primarily responsible for cell-cell interactions in white blood cells.
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The ________________ disease can result from an autoimmune response against collagen XVII or BP230.
The ________________ disease can result from an autoimmune response against collagen XVII or BP230.
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Which integrin is associated with leukocyte adhesion?
Which integrin is associated with leukocyte adhesion?
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What happens when talin binds to the β chain of an integrin?
What happens when talin binds to the β chain of an integrin?
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Integrin linkages depend solely on talin for proper function.
Integrin linkages depend solely on talin for proper function.
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Integrins switch conformations between _____ and _____ states based on external and internal signals.
Integrins switch conformations between _____ and _____ states based on external and internal signals.
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Match the following diseases with their associated integrin deficiencies:
Match the following diseases with their associated integrin deficiencies:
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What is one role of integrins in relation to cytoskeletal attachments?
What is one role of integrins in relation to cytoskeletal attachments?
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Cellular movement requires both the making and breaking of attachments mediated by integrins.
Cellular movement requires both the making and breaking of attachments mediated by integrins.
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What is the significance of the Ig superfamily of cell-adhesion molecules in integrin function?
What is the significance of the Ig superfamily of cell-adhesion molecules in integrin function?
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The binding protein that helps in the activation of integrins in platelets is called _____ .
The binding protein that helps in the activation of integrins in platelets is called _____ .
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What protein does activated Rap1 interact with to facilitate the recruitment of talin?
What protein does activated Rap1 interact with to facilitate the recruitment of talin?
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Talin interacts with actin and adaptor proteins only after being recruited by RIAM to the plasma membrane.
Talin interacts with actin and adaptor proteins only after being recruited by RIAM to the plasma membrane.
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What is the role of integrins in cell attachment?
What is the role of integrins in cell attachment?
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Talin unfolds to expose its binding sites for ______ and ______ upon recruitment.
Talin unfolds to expose its binding sites for ______ and ______ upon recruitment.
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Which of the following proteins is NOT mentioned as part of cell-matrix junctions?
Which of the following proteins is NOT mentioned as part of cell-matrix junctions?
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Integrins bind ligands with high affinity and low concentration on the cell surface.
Integrins bind ligands with high affinity and low concentration on the cell surface.
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Which complex serves as an organizing hub at many junctions involving integrins?
Which complex serves as an organizing hub at many junctions involving integrins?
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Anchorage dependence is primarily mediated by ______ and the intracellular signals they generate.
Anchorage dependence is primarily mediated by ______ and the intracellular signals they generate.
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Which of the following describes the function of focal adhesion kinase (FAK)?
Which of the following describes the function of focal adhesion kinase (FAK)?
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Match the following proteins with their roles in cell adhesion:
Match the following proteins with their roles in cell adhesion:
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Cells can grow and proliferate in culture without being attached to the extracellular matrix.
Cells can grow and proliferate in culture without being attached to the extracellular matrix.
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What happens to epithelial, endothelial, and muscle cells when they lose contact with the extracellular matrix?
What happens to epithelial, endothelial, and muscle cells when they lose contact with the extracellular matrix?
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The clustered FAK molecules phosphorylate each other on a specific ______, creating a docking site for signaling proteins.
The clustered FAK molecules phosphorylate each other on a specific ______, creating a docking site for signaling proteins.
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What is the role of kindlin in integrin activation?
What is the role of kindlin in integrin activation?
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Describe the Velcro principle in the context of integrin adhesion.
Describe the Velcro principle in the context of integrin adhesion.
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What role do integrins play in cells?
What role do integrins play in cells?
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Cell–matrix junctions do not respond to mechanical forces.
Cell–matrix junctions do not respond to mechanical forces.
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What are the two types of filaments integrins primarily connect to in cells?
What are the two types of filaments integrins primarily connect to in cells?
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Integrins are ________, which means they are composed of two different subunits.
Integrins are ________, which means they are composed of two different subunits.
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Match the following terms to their correct definitions:
Match the following terms to their correct definitions:
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What happens to the vinculin-binding sites in talin when it is stretched?
What happens to the vinculin-binding sites in talin when it is stretched?
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Anchorage dependence refers to the need for cells to be attached to a surface for growth and survival.
Anchorage dependence refers to the need for cells to be attached to a surface for growth and survival.
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Which protein is primarily responsible for the conformational switch of integrins from inactive to active?
Which protein is primarily responsible for the conformational switch of integrins from inactive to active?
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The ________ filaments in cell–matrix junctions provide contractile forces that affect junction stability.
The ________ filaments in cell–matrix junctions provide contractile forces that affect junction stability.
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What effect does attaching to a rigid matrix have on cell–matrix junctions?
What effect does attaching to a rigid matrix have on cell–matrix junctions?
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Signals from integrins only act in one direction, either outside-in or inside-out.
Signals from integrins only act in one direction, either outside-in or inside-out.
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What type of adhesion sites concentrate proteins containing phosphotyrosine?
What type of adhesion sites concentrate proteins containing phosphotyrosine?
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The process whereby cells respond to differences in the rigidity of the extracellular matrix is known as _________.
The process whereby cells respond to differences in the rigidity of the extracellular matrix is known as _________.
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Match the following functions to their respective proteins:
Match the following functions to their respective proteins:
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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.