Microtubules and Focal Adhesions Quiz
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Questions and Answers

What role do CLASPs play in relation to microtubules at focal adhesions?

  • They regulate focal adhesion turnover by sequestering GEF-H1.
  • They stimulate microtubule rescues to keep ends close to cortical capture sites. (correct)
  • They directly nucleate actin filaments through mDia.
  • They facilitate the disassembly of microtubules.
  • Which protein is responsible for capturing microtubules at cortical sites near focal adhesions?

  • RhoA
  • Kank proteins
  • LL5β (correct)
  • mDia
  • How do microtubules regulate Rho GTPases signaling?

  • By delivering relaxation factors to focal adhesions.
  • By sequestering GEF-H1, which activates RhoA. (correct)
  • By inhibiting the activity of myosin II.
  • By promoting the assembly of actin filaments.
  • What effect does GEF-H1 have on RhoA as a result of microtubule signaling regulation?

    <p>GEF-H1 activates RhoA, stimulating contractility through myosin II.</p> Signup and view all the answers

    Which of the following proteins cooperate to nucleate actin filaments?

    <p>APC and mDia</p> Signup and view all the answers

    Which proteins are responsible for the recycling and delivery of integrins within focal adhesions?

    <p>KIF1C and dynein</p> Signup and view all the answers

    What role do members of the RHO family of small GTPases play in cellular dynamics?

    <p>They interact with both actin and microtubule-associated proteins.</p> Signup and view all the answers

    How do microtubules influence actin dynamics within cells?

    <p>Through the local regulation of RHO GTPase activity.</p> Signup and view all the answers

    Which component is NOT directly linked to actin filaments at focal adhesions?

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

    Which protein recognizes growing microtubule ends and facilitates their assembly along actin fibers?

    <p>EB1/EB3</p> Signup and view all the answers

    What is the primary function of vinculin within focal adhesions?

    <p>To bind actin and talin, reinforcing tension.</p> Signup and view all the answers

    What is the significance of the mechanical support provided by the cytoskeleton in cell motility?

    <p>It leads to cooperative behavior of actin and microtubules.</p> Signup and view all the answers

    Which of the following proteins is involved in linking EB proteins to actin?

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

    What is the role of proteins like talin and vinculin in relation to the actin network?

    <p>They enable retrograde movement to become a protrusive force.</p> Signup and view all the answers

    Which mechanosensors are responsible for receiving mechanical stimulation from the extracellular matrix?

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

    What is the function of nesprins in the context of the nuclear envelope?

    <p>To span the nuclear envelope and connect with SUN proteins.</p> Signup and view all the answers

    What is primarily altered when force transmission affects the cytoskeletal networks?

    <p>The spatial organization of actin, microtubules, and intermediate filaments.</p> Signup and view all the answers

    Which proteins are considered major components of the nuclear lamina?

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

    How do LEM domain proteins interact with chromatin in the nucleus?

    <p>By interacting with the chromatin binding protein BAF.</p> Signup and view all the answers

    The molecular clutch is essential for which type of cellular movement?

    <p>Protrusive force generation at the leading edge.</p> Signup and view all the answers

    What is the relationship between actin networks and the extracellular matrix in terms of cell movement?

    <p>Actin networks transmit forces to reposition the ECM.</p> Signup and view all the answers

    What role do actin–microtubule crosslinking proteins play in stabilizing microtubules?

    <p>They stabilize microtubule ends and redirect growth along actin bundles.</p> Signup and view all the answers

    What is a consequence of the actin cortex acting as a physical barrier for microtubules?

    <p>It prevents microtubules from reaching the plasma membrane.</p> Signup and view all the answers

    How do protein complexes associated with cortical actin networks affect microtubules?

    <p>They capture both plus and minus ends of microtubules.</p> Signup and view all the answers

    What function do formins serve in relation to microtubules?

    <p>They promote local actin polymerization at microtubule ends.</p> Signup and view all the answers

    What happens during membrane protrusion events driven by actin polymerization?

    <p>Microtubules provide mechanical support against membrane retraction.</p> Signup and view all the answers

    What is a key characteristic of the relationship between actin and microtubules?

    <p>They interact to influence cellular structure and movement.</p> Signup and view all the answers

    What is the role of +TIPs in actin-microtubule interactions?

    <p>They help link actin bundles to growing microtubule ends.</p> Signup and view all the answers

    Which statement correctly describes the behavior of stiff microtubules in the cytoskeletal framework?

    <p>They provide mechanical support during membrane dynamics.</p> Signup and view all the answers

    What role does the extracellular matrix (ECM) play in relation to cytoskeletal components?

    <p>It affects the 3D organization of cytoskeletal components.</p> Signup and view all the answers

    Which cytoskeletal component is primarily involved in forming contractile structures within the cell?

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

    How does the aging process impact cell morphology according to the lecture?

    <p>Aging results in both morphometric and cytoskeletal alterations.</p> Signup and view all the answers

    What is the role of actin dynamics in cell morphology and movement?

    <p>Actin undergoes structural reorganization, facilitating cell movement.</p> Signup and view all the answers

    What type of actin architecture is commonly found in the lamellipodium of moving cells?

    <p>Branched networks</p> Signup and view all the answers

    Which component of the cytoskeleton is primarily responsible for providing mechanical strength to the cell?

    <p>Intermediate filaments</p> Signup and view all the answers

    How do extracellular cues affect actin assembly?

    <p>They are transmitted through membrane receptors to activate signaling pathways.</p> Signup and view all the answers

    Which cytoskeletal component is known for facilitating intracellular transport?

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

    What role does increased ECM stiffness play in progeria cells?

    <p>It contributes to increased RhoA activation.</p> Signup and view all the answers

    What is the consequence of the depletion of Histone Deacetylase (HDAC6) in senescent renal proximal tubule cells?

    <p>Impaired cell migration and increased cytoskeletal changes.</p> Signup and view all the answers

    Which factor is associated with the promotion of RhoA activation in progeria cells?

    <p>Elevated levels of reactive oxygen species (ROS).</p> Signup and view all the answers

    How are microtubules affected in fibroblasts from Hutchinson-Gilford progeria syndrome (HGPS) when treated with nocodazole?

    <p>They show increased resistance to nocodazole.</p> Signup and view all the answers

    What significant morphological change is observed in old human dermal fibroblasts compared to young ones?

    <p>Old cells are larger and less elongated.</p> Signup and view all the answers

    What does the aspect ratio of a cell indicate?

    <p>The symmetry of the cell shape.</p> Signup and view all the answers

    What is a common consequence of elevated RhoA expression in progeria cells?

    <p>Accelerated cellular senescence.</p> Signup and view all the answers

    What kind of structural changes occur in the cytoskeleton during cellular senescence?

    <p>Reorganization of the microtubule cytoskeleton.</p> Signup and view all the answers

    Study Notes

    Lecture 2: Cellular Microenvironment & Extracellular Matrix

    • Cellular microenvironment is a key focus.
    • Matrix components are crucial.
    • The 3D organization of matrix components is examined.
    • Physicochemical properties of the matrix and their relationship to aging are discussed.

    Lecture 3: Cell Morphometric Changes & Cytoskeletal Remodeling

    • Cytoskeletal components and their cross-talk regulate cell morphology.
    • The extracellular matrix (ECM) dictates the 3D organization of cytoskeletal components.
    • Cytoskeletal control of nuclear morphology is studied.
    • Cell morphometric and cytoskeletal alterations in aging are explored.

    Cytoskeletal Components and Cell Morphology

    • Actin, microtubules, and intermediate filaments are key cytoskeletal components.
    • These components play critical roles in cell morphology and function.
    • The cytoskeleton is a complex network of proteins that provides structural support, facilitates intracellular transport, and enables cell movement.

    Cytoskeletal Components (Detailed)

    • Actin filaments are involved in polymerization and depolymerization.
    • Microtubules are composed of alpha and beta-tubulin dimers.
    • Intermediate filaments are composed of various protein subunits.
    • The cytoskeleton plays multiple cellular roles, including mechanical strength, intracellular transport, and spatial organization.

    Cross-talk Between Actin and Microtubule Cytoskeletons

    • Microtubules can be guided by actin bundles.
    • Microtubule anchoring and stabilization from actin.
    • Actin acts as a physical barrier during microtubule growth.
    • Actin nucleation factors may initiate actin filament creation at microtubule ends.
    • Mechanical interaction occurs between microtubules and actin during membrane protrusions.

    Shared Regulators of Actin and Microtubule Dynamics

    • Rho family GTPases are shared regulators of actin and microtubule dynamics.
    • Rho GTPases interact with actin- and microtubule-associated proteins.
    • Microtubules can influence Rho GTPase activity locally.

    Cross-talk Between Actin and Microtubule Cytoskeleton at Focal Adhesions

    • Focal adhesions link the extracellular matrix to the actin cytoskeleton.
    • Integrins are critical for cell adhesion.
    • Recycling and new delivery of integrins depend on microtubule transport mechanisms.
    • Microtubule guidance and stabilization, along with signaling complex formation at microtubule ends, impact focal adhesions.
    • Micro-tubules are captured at focal adhesion-associated sites via CLASP family members and related proteins.

    Cell-Matrix and Cell-Cell Sensing: Common Mechanisms

    • Mechanical forces generated by actomyosin interactions are resisted by ECM and cell-cell adhesions.
    • This creates a tensional prestress in cells and tissues.
    • Actomyosin interactions, ECM, and cell-cell adhesions are crucial for structure and function.

    Cell Adhesion to the Matrix Shapes the Cell Nucleus

    • Nascent adhesions form at the leading edge of cell protrusions.
    • These adhesions involve multiple ligand-bonded integrins and related proteins.
    • Adhesome proteins, including vinculin, are recruited for tension- and/or tension-independent processes.
    • The actin network interacts with proteins controlling adhesion to convert forces.

    Extracellular Matrix Control of Nuclear Morphology and Position

    • Mechanical stimulation from the ECM influences cytoskeletal network organization.
    • Force transmission alters cytoskeletal network organization via integrins.
    • Nesprins and SUN domain proteins integrate cell-matrix forces with nuclear organization.
    • The nuclear lamina is crucial for force transmission to the nucleus, influencing gene expression.
    • Diverse factors connect the inner nuclear membrane to the cytoskeleton.
    • Kinesin-1, dynein, and other proteins bridge these components.
    • Interaction sites exist at microtubules and intermediate fibers for cell cycle progression and other cellular processes.

    Experiments to Demonstrate Prestressed Nuclear Architecture in Living Cells

    • Experiments demonstrate nuclear architecture impacts force balance in living cells.
    • Force balance changes can be studied with different cytoskeletal factors.
    • This research focuses on how isolated nuclei respond to force.

    Cytoskeleton Organization is Dependent on Cell Microenvironment Interaction

    • Cytoskeleton organization shifts in response to varying microenvironments.
    • Cell adhesion dynamics are crucial.
    • Focal Adhesions, stabilization, and nascent adhesions influence the cytoskeleton.

    Fragmentation of Collagen Fibrils within Aged/Photoaged Skin Causes Collapse of Fibroblasts

    • Collagen fragmentation correlates with aged skin fibroblast collapse.
    • Mechanical tension is crucial for fibroblast health and dermal structure.
    • Loss of structure can affect collagen synthesis and fibroblast response.

    The Proposed Model for RhoA/Sun2-Mediated Increase of Cytoskeletal Stiffness in Progeria Cells

    • The ECM, cytoskeleton, and nucleoskeleton are connected.
    • Increased ECM stiffness correlates with RhoA activation and cytoskeleton stiffness.
    • RhoA activation correlates with ROS production, inflammation, and DNA damage.

    Cellular Senescence is Associated with Reorganization of the Microtubule Cytoskeleton

    • HDAC6, Rock1, and γ-tubulin depletion impacts senescent cells.
    • Senescent cells show microtubule stabilization, and impaired cell migration.

    Imbalanced Nucleo-Cytoskeletal Connections

    • Imbalanced nucleo-cytoskeletal connections lead to polarity defects in progeria and aging.
    • Nesprin-2G, SUN1, and SUN2 interact with microtubules to affect cell signaling and shape.

    Biological Age-Dependent Changes of Cell Morphology

    • Cellular morphology alters with age.
    • Cell size, shape, and cellular traction force change between young and older cells.

    Age-Dependent Alteration of Nuclear Morphology

    • Nucleus size and shape change with age in fibroblasts.
    • Nucleus area, parameters and aspects are different between young and old cells.

    Age-Dependent Alteration of Cell Motility

    • Cell motility declines with age and is linked to functional and molecular alterations.
    • Cell trajectories and total cell distance correlate with age and cell type.

    Heterogeneity in Cellular Mechanical Responses with Aging

    • Cellular response and aging have functional heterogeneity.
    • Biophysical parameters vary in a group of cells according to chronological age.

    Heterogeneity in Cellular Functional Responses with Aging

    • Cellular responses display variability with age in physiological processes.
    • Diverse molecular responses, including ATP production, influence age-related changes.

    Mechanobiological Changes in Aging

    • Cellular response to mechanical stress changes with aging.
    • ECM, cytoskeleton, and cell mechanics all change in function with age.
    • These changes include ECM crosslinking and stiffness, actin polymerization, and cell mechanics.

    Lecture 4: Proteostasis

    • Proteostasis maintains cellular protein homeostasis efficiently in cells.
    • This includes the folding, refolding, and degradation of proteins in cells.
    • Cellular processes such as protein homeostasis, folding and degradation are altered by aging and stressors.

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    Description

    Test your knowledge on the interaction between microtubules and focal adhesions. This quiz covers key proteins involved in cellular dynamics, the role of Rho GTPases, and the importance of the cytoskeleton in cell motility. Dive deep into the mechanisms that regulate these complex processes.

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