Retta - L20

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Questions and Answers

What specific apoptotic process occurs when adherent cells detach from the substrate?

Necrosis

Autophagy

Caspase-mediated apoptosis

Anoikis (correct)

Which protein is involved in mediating the crosstalk between cadherins and integrins?

FAK

Rap1 (correct)

PI3Kinase

Src Kinase

Which property allows E-cadherin to function correctly in cell adhesion?

Calcium ion dependency (correct)

GDP binding

Phosphorylation of its cytoplasmic domain

Interactions with integrins

What regulates the cytoskeleton dynamics in the crosstalk between cadherins and integrins?

Rho GTPase Signup and view all the answers

Which mechanism best describes the process of β-catenins translocating to the nucleus?

Cytoplasm-to-nucleus shuttling Signup and view all the answers

What is the primary role of catenins in the context of cadherins?

Connecting cadherins to actin filaments of the cytoskeleton Signup and view all the answers

How do cadherins and growth factor receptors interact functionally?

They cooperate to trigger specific intracellular signaling events Signup and view all the answers

What structural property distinguishes integrins?

They are formed as α and β heterodimers Signup and view all the answers

What role do integrins play in cellular processes?

Connecting to the extracellular matrix and regulating signaling pathways Signup and view all the answers

Which of the following best describes the interaction between cadherins and the cytoskeleton?

The interaction is mediated by adaptor proteins specifically to actin filaments Signup and view all the answers

Which of the following best describes the role of E-cadherin in embryonic development?

It supports the implantation of the embryo. Signup and view all the answers

What is the primary function of non-classical cadherins such as T-cadherin?

They have no adhesive function and their role is unclear. Signup and view all the answers

How does the presence of calcium ions influence the function of cadherins?

Calcium ions stabilize the conformation of cadherins, enabling adhesion. Signup and view all the answers

Which of the following cadherins is specifically expressed in endothelial cells and is vital for blood vessel formation?

VE-cadherin Signup and view all the answers

What type of adhesion do cadherins primarily mediate?

Homophilic adhesion Signup and view all the answers

What structural feature distinguishes cadherins as single pass proteins?

They span the plasma membrane only once. Signup and view all the answers

How does calcium influence cadherin function?

Calcium modulates the conformation affecting cell-cell junctions. Signup and view all the answers

What happens to cadherin expression during the formation of the neural tube?

There is a shift from E-cadherin to N-cadherin expression. Signup and view all the answers

How can cadherins facilitate cell sorting after dissociation?

By interacting preferentially with the same types of cadherins. Signup and view all the answers

What can be concluded about the role of glycoproteins in cadherins?

Glycoproteins contribute to the overall stability of cadherin structure. Signup and view all the answers

What effect does the application of calcium chelators have on epithelial cells?

They promote the dissociation of epithelial tissues. Signup and view all the answers

In the context of morphogenetic events, what is suggested by the exchange of E-cadherin to N-cadherin?

It signifies the onset of differentiated migratory behavior in cells. Signup and view all the answers

What is the main function of VE-cadherin in relation to β-catenin?

VE-cadherin modulates the function of β-catenin, influencing gene expression. Signup and view all the answers

Which cadherins mediate the formation of desmosomes?

Non-classical cadherins Signup and view all the answers

How does tension contribute to the stability of adherent junctions?

Tension induces the recruitment of additional cadherins. Signup and view all the answers

What is the primary structural role of intermediate filaments in desmosomes?

They provide mechanical strength. Signup and view all the answers

What characterizes the interaction of non-classical cadherins in desmosomes?

They mediate homophilic interactions. Signup and view all the answers

Which of the following is NOT a component of hemidesmosomes?

Cadherins Signup and view all the answers

What determines the strength of adherent junctions as described in the content?

The number of cadherins recruited to the junction. Signup and view all the answers

Which proteins serve as adaptor proteins specific to desmosomes?

Desmoplakin, plakoglobin, and plakophilin Signup and view all the answers

In adherent junctions, how does the organization of the actin cytoskeleton contribute to morphology?

It forms an adhesion belt that shapes cells during morphogenesis. Signup and view all the answers

What is a significant outcome of the epithelial to mesenchymal transition in carcinoma development?

Acquisition of a migratory phenotype Signup and view all the answers

Which cadherin is typically expressed in epithelial cells before the transition to a mesenchymal phenotype?

E-cadherin Signup and view all the answers

How do cadherins contribute to cell behavior beyond adhesion?

By mediating signal transduction Signup and view all the answers

What characterizes the shift in cadherin expression during epithelial to mesenchymal transition?

From E-cadherin to N-cadherin Signup and view all the answers

Which protein family is crucial for linking cadherins to the actin cytoskeleton?

Catenin family Signup and view all the answers

What role does vascular endothelial cadherin (VE-cadherin) play in endothelial cells?

Maintaining cell-cell adhesion Signup and view all the answers

Which molecular event is associated with cadherins that affects signal transduction?

Interaction with Protein Tyrosine Phosphatase Signup and view all the answers

Which transformation occurs in epithelial cells during the epithelial to mesenchymal transition?

Loss of cell-cell contact Signup and view all the answers

What is the primary function of Rho GTPase in the context of cadherin involvement?

Modulating cytoskeletal dynamics Signup and view all the answers

What is the primary consequence of abnormal detachment of adherent cells from their substrate?

Initiation of apoptosis through anoikis Signup and view all the answers

How does Rap1 facilitate the interaction between cadherins and integrins?

By enhancing cell matrix adhesion upon dissociation of cell-cell junctions Signup and view all the answers

What role do reactive oxygen species play in the crosstalk between cadherins and integrins?

They modulate the activity of multiple proteins involved in signaling Signup and view all the answers

What is the significance of β-catenin in the context of cadherins and gene transcription?

It translocates to the nucleus to act as a transcription co-factor Signup and view all the answers

What is a characteristic feature of cadherins that differentiates them from other adhesion molecules?

Their dependence on calcium ions for correct folding and function Signup and view all the answers

What is the primary function of catenins in relation to cadherins?

To act as a structural bridge to the actin cytoskeleton Signup and view all the answers

What is the primary tissue type associated with P-cadherin?

Placenta and epidermis Signup and view all the answers

Which mechanism describes the interaction between cadherins and growth factor receptors?

They cooperate in transducing signaling related to growth factors Signup and view all the answers

Which type of cadherin is specifically known to be involved in adherent junctions in endothelial cells?

VE-cadherin Signup and view all the answers

What role do integrins play that is similar to cadherins?

They connect to the extracellular matrix and also regulate signaling pathways Signup and view all the answers

Which characteristic distinguishes integrins from cadherins?

Integrins are α and β heterodimers while cadherins do not have multiple subunits Signup and view all the answers

What is the effect of altering classic cadherins in embryonic development?

Prevention of embryo implantation Signup and view all the answers

In what way do cadherins and integrins interact with their respective cytoplasmic domains?

Both interactions rely on adaptor proteins that attach them to the cytoskeleton Signup and view all the answers

Which statement best describes the role of calcium ions in cadherin function?

Calcium ions are critical for the proper folding of the extracellular domain of cadherins. Signup and view all the answers

Which cadherin type is specifically associated with structural disease when altered?

Desmoglein Signup and view all the answers

What is the impact of calcium on cadherin-mediated cell-cell junctions?

Calcium modulation can strengthen cell-cell junctions. Signup and view all the answers

During the differentiation of epithelial cells in the neural tube, which cadherins undergo a shift in expression?

E-cadherin to N-cadherin. Signup and view all the answers

What is a consequence of dissociating cells expressing different types of cadherins?

Cells expressing the same cadherins will sort and associate with each other. Signup and view all the answers

How does the presence of glycoprotein components influence cadherins?

Glycoprotein sugar residues contribute to the functional diversity of cadherins. Signup and view all the answers

What would happen if calcium ions are chelated in epithelial tissues?

Dissociation of epithelial tissues would occur. Signup and view all the answers

Which observation can be made regarding cadherin dynamics during cell movement?

Cadherin accumulates at cell junctions as cells form adhesions. Signup and view all the answers

What does the differential expression of cadherins during embryogenesis suggest?

Cell recognition and sorting are crucial for tissue formation. Signup and view all the answers

What change in cadherin expression is a major marker of epithelial to mesenchymal transition?

Shift from E-cadherin to N-cadherin Signup and view all the answers

Which proteins are primarily involved in the regulation of adhesive functions of cadherins?

Catenins Signup and view all the answers

During the epithelial to mesenchymal transition, which phenotype do epithelial cells lose?

Epithelial characteristics Signup and view all the answers

Which of the following is NOT a function of VE-cadherins?

Activating matrix metalloproteinases Signup and view all the answers

What physiological process does the epithelial to mesenchymal transition also partake in besides tumorigenesis?

Embryonic development Signup and view all the answers

The presence of which signaling molecule is essential for the functions of VE-cadherins?

Vascular endothelial growth factor Signup and view all the answers

What occurs to the cytoskeletal organization during the epithelial to mesenchymal transition?

Increase in actin stress fibers formation Signup and view all the answers

Which protein family is crucial for linking cadherins to the actin filaments?

Catenins Signup and view all the answers

What morphological change occurs in cells as they transition from epithelial to mesenchymal phenotype?

Acquisition of migratory traits Signup and view all the answers

What is a key characteristic that differentiates adherent junctions from desmosomes?

Adherent junctions participate in cellular signaling. Signup and view all the answers

Which of the following best describes the process by which cadherins strengthen cell-cell adhesion?

Formation of homophilic interactions among cadherins. Signup and view all the answers

What role does tension from the actin cytoskeleton play in adherent junctions?

It helps stabilize and strengthen cell-cell junctions. Signup and view all the answers

Which specific adaptor proteins are uniquely involved in linking non-classical cadherins to the cytoskeleton in desmosomes?

Desmoplakin, plakoglobin, and plakophilin. Signup and view all the answers

How does the presence of VE-cadherin influence signal transduction in endothelial cells?

It modulates β-catenin function affecting gene expression. Signup and view all the answers

What morphological structure is formed by the actin cytoskeleton in the presence of cadherins, especially in epithelial cells?

Adhesion belts. Signup and view all the answers

Which mechanism describes how cadherins influence morphogenetic events during tissue remodeling?

By contracting actin-myosin networks that induce shape changes. Signup and view all the answers

What outcome can result from alterations in desmosomal cadherins such as desmoglein and desmocolin?

Severe skin blistering and tissue fragility. Signup and view all the answers

In the context of cell-matrix interactions, what role do integrins play?

They mediate the attachment of cells to the extracellular matrix. Signup and view all the answers

Study Notes

Cell-Cell Junctions: Cadherins

Cadherins are adhesive proteins crucial for cell-cell adhesion, forming dimers on the plasma membrane.
Interaction with neighboring cell cadherins and actin filaments is mediated by adaptor proteins known as catenins (α, β, p120).
Cadherins not only provide structural support but also participate in signaling transduction linked to growth factor receptors.
These proteins can regulate signaling pathways through tyrosine kinases, facilitating molecular crosstalk between cadherins and growth factor receptors.

Integrins: Structure and Function

Integrins are α and β heterodimers functioning as transmembrane receptors that connect to extracellular matrix (ECM) proteins.
Their cytoplasmic domains interact with various adaptor proteins that link them to the actin cytoskeleton.
Integrins have a key role in signaling pathways, including PI3Kinase, Src, and focal adhesion kinase (FAK), influencing processes such as cell proliferation and migration.
Anoikis refers to apoptosis occurring in adherent cells that detach from the extracellular matrix, highlighting the importance of integrins for cell survival.

Molecular Crosstalk Between Cadherins and Integrins

Rap1, a small GTPase, mediates the interaction between cadherins and integrins, strengthening cell-matrix adhesions when cell-cell junctions are compromised.
This cross-talk is influenced by growth factor receptors, allowing complex regulatory pathways that affect gene expression and signaling.

Reactive Oxygen Species and Crosstalk

Rho GTPase modulates cytoskeleton dynamics, participating in the cadherin-integrin signaling nexus.
Reactive oxygen species (ROS) play a vital role in this crosstalk, being sensitive to oxidative-reductive changes, thus coordinating multiple regulatory proteins.

Cadherins: A Diverse Family of Molecules

Cadherins require calcium ions for proper function and folding of their extracellular domain, facilitating homophilic interactions.
Classical cadherins encompass E-cadherin (epithelial), N-cadherin (neuronal), and P-cadherin (placental).
Non-classical cadherins include desmosomal cadherins and protocadherins, with various tissue specificities.

Functional Roles of Cadherins

E-cadherin is vital for embryo implantation; absence leads to developmental failure.
N-cadherin is important for neuronal connections and muscle cell adherence; mutations can result in embryonic lethality.
P-cadherin is linked to epidermal and placental development; its mutation affects mammary gland structure but is less lethal than E- or N-cadherin.

Cadherin-Mediated Homophilic Adhesion

Cadherins mediate homophilic adhesion, meaning they bind to identical proteins on adjacent cells.
Heterophilic adhesion refers to the interaction between different protein types, such as selectins.

Cadherins and Calcium Dependency

The structure of cadherins changes without sufficient calcium, compromising cell-cell junction integrity.
Calcium chelators can disrupt junctions and are useful in experimental studies to analyze adhesion dynamics.

Developmental Role of Cadherins

During embryogenesis, cadherins drive cell differentiation and organization, such as the transition from E-cadherin to N-cadherin during neural tube formation.
Cadherin expression changes coincide with morphogenetic events, influencing cell migration and tissue formation.

Cadherin-Dependent Cell Sorting

Cadherins facilitate sorting of cells based on adhesive specificity through reassociation of cells expressing similar cadherins.
Experimental manipulation of cadherin levels can be employed to study tissue organization and adhesion properties.

Monitoring Cadherin Dynamics

Fluorescent tagging (e.g., GFP cadherin) enables visualization of cadherin dynamics and interactions in live cell studies.
Video microscopy can be used to track protein distribution and behavior at cell junctions, providing insights into the adhesion process.### Cadherins and Epithelial Cell Behavior
Cadherins localize at the plasma membrane, forming cell-cell junctions when cells are closely packed.
Diffused cadherins in the cytoplasm are targeted for degradation in the proteasome.
Synthesis and localization of new cadherins to the plasma membrane are essential when cells are not attached.

Epithelial-Mesenchymal Transition (EMT)

EMT is significant in cancer, particularly in carcinoma development from epithelial tissues.
Normal epithelial cells can undergo morphological changes to acquire a mesenchymal phenotype.
Characterized by the loss of tight cell-cell contacts and the ability to interact with the extracellular matrix via integrins.
Transition is marked by a shift from E-cadherin in epithelial cells to N-cadherin in mesenchymal cells.
EMT occurs during embryonic development and is also a hallmark of tumor genesis.

Role of the Cytoskeleton in EMT

Cytoskeletal reorganization is crucial for morphological changes during EMT.
Actin stress fibers and intermediate filaments form connections that influence cell shape and adhesion.
Signaling events mediate the transition, altering cadherin expression and cellular behavior.

Cadherin Functions and Interactions

Cadherins, along with catenins (p120, β-catenin, and α-catenin), connect to the actin cytoskeleton, playing roles in adhesion and signaling.
Rho GTPase is involved in actin cytoskeleton regulation, connecting to cadherins' adhesive functions.
VE-cadherin, specific to endothelial cells, functions similarly to cadherins in epithelial cells, mediating cell adhesion and signal transduction.

Adherent Junctions and Mechanical Forces

Initial cell-cell contact through few cadherins expands to stronger adhesion by recruiting more cadherins and catenins.
Tension in cell-cell junctions strengthens adhesion, promoting enhanced interaction through actin filament dynamics.
Adjustments in junction strength are tied to cellular movement and tension.

Desmosomes and Hemidesmosomes

Desmosomes connect cells with non-classical cadherins and provide mechanical strength through intermediate filaments.
Hemidesmosomes, mediated by integrins, anchor cells to the extracellular matrix, interacting with laminin.
Both junction types play crucial roles in maintaining tissue integrity by anchoring epithelial cells.

Tight Junctions

Tight junctions act as barriers, preventing solute passage between cells; they require transport systems to move solutes.
Composed of claudins and occludins, tight junctions form molecular seals through transmembrane protein interactions.
Zonula occludens (ZO) proteins anchor tight junctions to the actin cytoskeleton.

Gap Junctions

Gap junctions facilitate metabolic and electrical coupling between cells, allowing small molecules (under 1 kDa) to pass.
Formed by connexins, the channels (connexons) enable communication and coordination among adjacent cells.

Pathogen Transmigration

Pathogens may utilize paracellular or transcellular routes to traverse epithelial barriers.
Paracellular route involves breaching cell junctions, while transcellular route requires entering one cell and exiting through the base.### Intracellular Mediators and Cell Communication
c-AMP and I3P are important intracellular mediators that facilitate rapid metabolic and signaling connections between cells.
Animal cells communicate predominantly through gap junctions, which are specialized channels that allow the passage of small molecules and ions.

Gap Junction Structure

Gap junctions consist of connexons, each formed by six connexin subunits.
Connexons can form heteromeric or homomeric structures, leading to either homotypic or heterotypic intercellular channels.
In humans, there are 14 distinct connexins available for forming these channels.

Functions of Gap Junctions

Gap junctions enable electrical coupling in nerve cells, allowing rapid propagation of action potentials compared to chemical synapses.
They are critical for the synchronization of contractions in heart muscle cells and smooth muscle cells responsible for intestinal peristalsis.
Major roles include regulating vascular tone and mediating communication during embryogenesis and in normal ovarian follicle development.

Regulation of Gap Junctions

The opening and closing of gap junctions can be modulated by various signals, such as neurotransmitters.
Dopamine decreases gap-junction communication in retinal neurons by reducing c-AMP diffusion among them.

Cell Junction Types Overview

Tight junctions: Seal neighboring cells in epithelial layers to prevent molecule leakage.
Adhesion junctions: Connect actin bundles between adjacent cells.
Desmosomes: Link intermediate filaments between cells.
Gap junctions: Permit the passage of ions and small water-soluble molecules.
Hemidesmosomes: Anchor cells to the basal lamina.
Focal adhesions: Mediate interactions between cells and the extracellular matrix, composed primarily of integrins.

Selectins and Transient Cell Adhesion

Selectins are adhesion proteins that facilitate transient interactions in the bloodstream, particularly during inflammation.
They assist in the extravasation process of white blood cells exiting the bloodstream to reach damaged tissues.
Different types of selectins include L-selectin (on white blood cells), P-selectin (on platelets and activated endothelial cells), and E-selectin (on activated endothelial cells).

Mechanism of White Blood Cell Extravasation

Initial adhesion between white blood cells and endothelial cells is weak and mediated by selectins.
This weak adhesion allows leukocytes to roll along the endothelial surface, leading to stronger adhesion through integrins once activated.
Integrins then mediate firm adhesion to endothelial cells, allowing white blood cells to migrate through the endothelial layer into tissues.

Overall Summary of Leukocyte Adhesion

The process unfolds in a sequence: weak interactions by selectins, triggering integrin activation, and concluding with strong adhesion facilitating leukocyte passage.
Chemotaxis from inflamed tissues directs leukocyte activation and migration, highlighting the role of selectins in immune response dynamics.