Cell-Matrix Junctions: Integrins Overview

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Questions and Answers

What is the primary role of integrins in the context of cell-matrix junctions?

To act as receptors for proteins on the cell surface

To transmit mechanical and molecular signals between the matrix and the cytoskeleton (correct)

To facilitate nutrient transport across the membrane

To solely provide structural support to the cell

Which statement accurately describes the structural characteristics of integrins?

Integrins consist of two glycoprotein subunits, α and β (correct)

Integrins are composed of three noncovalently associated subunits

Integrins are exclusively found in epithelial cells

Integrins only have intracellular C-terminal tails

Which molecules primarily bind to integrins on the surface of animal cells?

Intracellular signaling proteins

Transmembrane proteoglycans

Extracellular matrix proteins (correct)

Cadherins

What effect does tension have on integrins during cellular signaling?

It causes integrins to loosen their grip on their binding partners Signup and view all the answers

What is the consequence of integrin binding to an extracellular matrix component?

It sends a signaling message into the interior of the cell Signup and view all the answers

Which type of cells are integrins particularly crucial for in their interactions with the extracellular matrix?

Epithelial cells and connective-tissue cells Signup and view all the answers

How do integrins contribute to the organization of the extracellular matrix?

By transmitting signals that regulate cell behavior regarding the matrix Signup and view all the answers

What role do transmembrane proteoglycans play in relation to integrins?

They can function as matrix receptors or co-receptors Signup and view all the answers

What role does the β2 subunit primarily play on white blood cells?

It helps white blood cells fight infection by mediating cell–cell interactions. Signup and view all the answers

What sequence is best understood for integrin binding in extracellular matrix proteins?

Arg-Gly-Asp (RGD) Signup and view all the answers

What happens to white blood cells in individuals with leukocyte adhesion deficiency?

They synthesize non-functional integrins. Signup and view all the answers

Which process allows integrins to switch from inactive to active states?

A major conformational change within the integrin structure. Signup and view all the answers

Which component forms a crucial link between integrins and the actin cytoskeleton?

Talin Signup and view all the answers

What is the primary role of integrins in animal cells?

To provide transmembrane linkages between the extracellular matrix and the cytoskeleton Signup and view all the answers

Which ion's concentration influences the binding of integrins to their extracellular ligands?

Ca2+ Signup and view all the answers

Which of the following ligands do β3 integrins primarily bind to?

Fibrinogen Signup and view all the answers

What is the consequence of Glanzmann disease in humans?

Defective clotting and excessive bleeding. Signup and view all the answers

What is the fate of mutant mice unable to produce β1 integrins?

Die early in embryonic development Signup and view all the answers

How do changes in mechanical tension affect cell–matrix junctions?

They recruit additional integrins to strengthen the junction. Signup and view all the answers

Which proteins are concentrated at focal adhesions due to the activity of FAK and Src family kinases?

Proteins containing phosphotyrosine Signup and view all the answers

Which integrin is primarily involved in linking hemidesmosomes to laminin?

α6β4 Signup and view all the answers

What typically triggers the 'inside-out' activation of integrins?

Intracellular regulatory signals promoting protein interactions. Signup and view all the answers

What potential disease is caused by defects in collagen type XVII or BP230?

Bullous pemphigoid Signup and view all the answers

How do integrins respond to the presence of a ligand in their active state?

They can extend to bind matrix proteins firmly. Signup and view all the answers

What is an effect of integrin activation when they bind to extracellular matrix ligands?

They initiate a conformational change leading to signal transduction Signup and view all the answers

What is one way that the outside-in signaling mechanism functions?

By utilizing matrix proteins to trigger intracellular changes. Signup and view all the answers

Which adaptor protein links integrins to actin filaments?

Talinin Signup and view all the answers

Which integrin type is associated with bleeding disorders due to no platelet aggregation?

αIIbβ3 Signup and view all the answers

What do cytoplasmic adaptor proteins do in relation to integrins?

They allow attachment of actin filaments to integrins. Signup and view all the answers

Which of these integrins is known to interact with multiple ligand types, including laminins?

α6β1 Signup and view all the answers

What aspect of their structure allows talin to act as a tension sensor?

It consists of multiple folded protein domains that unfold under tension. Signup and view all the answers

What happens to talin upon recruitment by RIAM to the plasma membrane?

It unfolds to expose binding sites for integrin and actin. Signup and view all the answers

Which protein is involved in triggering integrin activation alongside talin?

Kindlin Signup and view all the answers

Which proteins are involved in the intracellular attachment of α6β4 integrins to keratin filaments?

Plectin and BP230 Signup and view all the answers

What type of junctions can sense and respond to mechanical forces?

Both cell–cell and cell–matrix junctions Signup and view all the answers

What structural feature characterizes the inactive state of integrins?

The dimeric structure is folded into a compact form. Signup and view all the answers

What happens to talin when mechanical tension is applied?

It unfolds and exposes binding sites for vinculin Signup and view all the answers

Which method has contributed to our understanding of integrin structure and activity states?

Electron microscopy and x-ray crystallography. Signup and view all the answers

What is the main role of integrins in relation to the extracellular matrix?

To control cell behavior via intracellular signaling pathways. Signup and view all the answers

What role does kindlin play related to integrins?

Binds to the integrin β-subunit's cytoplasmic tail Signup and view all the answers

What term describes the phenomenon where cells rely on attachment to the extracellular matrix for survival and growth?

Anchorage dependence Signup and view all the answers

Which of the following statements about integrins is false?

Integrins only exist in inactive states. Signup and view all the answers

What type of integrin is referred to as LFA1?

αLβ2 Signup and view all the answers

Which integrin is associated with leukocyte adhesion deficiency (LAD)?

αLβ2 Signup and view all the answers

Why is the clustering of integrins important after their activation?

It forms a dense plaque anchoring multiple integrin molecules. Signup and view all the answers

What type of structural arrangement do integrins exhibit based on their subunits?

Dimeric configuration Signup and view all the answers

Which component is not typically involved in the strengthening of cell–matrix junctions?

Cadherins Signup and view all the answers

What occurs to the tails of the β chain during the transition from inactive to active integrin states?

They unhook to expose binding sites. Signup and view all the answers

Which of the following components serves as an organizing hub at many junctions formed by integrins?

Integrin-linked kinase (ILK) Signup and view all the answers

In relation to integrin activation, what is the role of talin?

It facilitates integrin activation by unhooking the β chain. Signup and view all the answers

How do integrins influence cell behavior?

They impact processes such as proliferation and migration. Signup and view all the answers

The integrin α5β1 primarily binds to which extracellular matrix protein?

Fibronectin Signup and view all the answers

What is the role of focal adhesion kinase (FAK) at cell-matrix junctions?

To phosphorylate proteins and facilitate signaling. Signup and view all the answers

What results from tissue rigidity in relation to cell–matrix junctions?

Increased mechanical tension prompting a cellular response Signup and view all the answers

What is a significant function of the integrin-binding sequences in extracellular matrices?

Mediating cell adhesion Signup and view all the answers

Which functional aspect of integrins is associated with anchorage dependence in cells?

Connection to cytoskeletal structures Signup and view all the answers

Which cytoplasmic protein is known for its role in integrin signaling through tyrosine phosphorylation?

Focal adhesion kinase (FAK) Signup and view all the answers

What aspect of integrins differentiates them from other cell-surface receptors?

They usually bind ligands with lower affinity at higher concentrations. Signup and view all the answers

How do integrins and conventional signaling receptors work together?

They often cooperate to drive cell proliferation and survival. Signup and view all the answers

What effect does losing contact with the extracellular matrix have on some cell types?

They undergo apoptosis. Signup and view all the answers

What structure is formed when integrins cluster at cell-matrix contacts?

Focal adhesions Signup and view all the answers

What is the main function of talin in cell-matrix adhesion complexes?

To link integrins to the actin cytoskeleton. Signup and view all the answers

Study Notes

Cell-Matrix Junctions: Integrins and Signaling

Cells interact with the extracellular matrix (ECM) through transmembrane proteins, primarily integrins. These proteins act as receptors, linking the ECM to the cytoskeleton. Their role extends beyond just attachment, influencing cell behavior.
Integrins are transmembrane heterodimers (α and β subunits). Extracellular domains bind specific ECM protein sequences (e.g., RGD, LDV) in fibronectin, laminin, and collagen.
Intracellular domains of integrins link to the cytoskeleton (mostly actin filaments, but also keratin filaments in hemidesmosomes). Adaptor proteins (e.g., talin, vinculin, plectin) mediate this connection.
Integrins can switch between active and inactive conformations. The inactive state is compact, while the active state is extended.
Active state: External ligand binding leads to internal cytoskeletal attachment.
Inactive state: Integrins are closed, and internal attachment points are hidden.
Integrin activation is regulated by "outside-in" (ECM signal causing cytoskeletal attachment) and "inside-out" (intracellular signals affecting ECM binding) mechanisms.
Outside-in signaling: Ligand binding exposes cytoskeletal binding sites.
Inside-out signaling: Intracellular signals (like thrombin signaling in platelets) affect integrin's ability to bind to ECM ligands.

Integrin Function in Specific Cell Types

Epithelial cells: Hemidesmosomes anchor cells to the basal lamina (via laminin) using α6β4 integrins, linked to keratin filaments.
Connective tissue cells: Integrins mediate interactions with surrounding ECM.
Fibroblasts: Create focal adhesions when attached to rigid surfaces.
Muscle cells: α7β1 integrins form myotendinous junctions, attaching muscles to tendons.
Leukocytes (white blood cells): β2 integrins (e.g., αLβ2/LFA-1) for cell-cell adhesion, crucial for immune response; deficiencies lead to severe infections (leukocyte adhesion deficiency).
Platelets: β3 integrins (e.g., αIIbβ3) are crucial for blood clotting; deficiencies cause bleeding disorders (Glanzmann disease).
Integrin mutations cause severe consequences. Defects in subunits result in specific conditions.

Integrin Clustering and Mechanotransduction

Integrins cluster to form robust cell-matrix adhesions.
Signaling proteins (e.g., FAK, ILK) are recruited to these adhesion sites.
FAK, a tyrosine kinase, acts as a key signaling hub, initiating intracellular cascades that control many aspects of cell function.
Cell-matrix adhesions can sense and respond to mechanical forces.
Integrins and associated proteins, like talin, can act as mechanotransducers, sensing forces on the junction to strengthen attachments..
Changes in force cause shifts, changing their ligand-binding capacity or ability to interact with intracellular proteins, and triggering the formation of more robust attachments. This allows cells to respond to tissue stiffness.

Anchorage Dependence

Cell attachment to the ECM is essential for cell growth, proliferation, and survival (anchorage dependence).
Cells deprived of ECM undergo apoptosis.
Disruptions in anchorage dependence mechanisms are implicated in cancer cell invasiveness.

Integrin Signaling Pathways

Integrins activate intracellular signaling pathways, working with other receptor types.
The Ras-MAP kinase pathway, and other pathways are regulated by both integrins and other receptors together.

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Description

Explore the complex role of integrins in cell-matrix junctions. This quiz covers how integrins function as receptors linking the extracellular matrix to the cytoskeleton, their structural components, and the transition between active and inactive states. Test your knowledge on integrin-mediated signaling and cellular behavior.