Chapter_11_Cell_Adhesion_and_Communication_S25__1_

Chapter 11: ECM and Cell Signaling

Extracellular Matrix (ECM)

• Definition: The ECM is a complex network of proteins and carbohydrates that surrounds cells.

• Components:

  • Collagen: Major fibrous protein, about one-third of protein in the body.

    • Provides structural support.

  • Proteoglycans: Composed of proteins and polysaccharides; serve as a filler within the matrix.

    • Contribute to the resilience of the ECM by resisting compression and tension.

  • Function: Provides structure, support, and facilitates communication between cells.

Collagen

• Synthesis: Produced in the rough ER, processed in the Golgi apparatus, and secreted by exocytosis.

• Structure: Consists of long chains where glycine is the third amino acid in the chain, often accompanied by proline residues.

Proteoglycans

• Structure: Comprises a core protein and attached polysaccharide chains.

• Importance: They are essential for cell adhesion, integrity of the ECM, and interacting with various signaling molecules.

ECM and Cytoskeleton Interaction

• Integral Membrane Proteins: Include integrins, which connect the ECM to the actin filaments of the cytoskeleton.

• Function:

  • Help maintain cell positioning.

  • Facilitate cell adhesion and coordination.

  • Loss of integrin activity can lead to issues such as cancer metastasis.

Cell-Cell Adhesion

• Types:

  • Direct Adhesion:

    • Tight Junctions: Create watertight seals between adjacent cells; formed by proteins that stitch membranes together (e.g., in intestinal epithelial cells).

    • Desmosomes and Adherens Junctions: Provide strong adhesion through cadherins that connect to intermediate filaments or actin filaments, respectively.

    • Gap Junctions: Allow for direct communication between cells by connecting intracellular spaces.

Cadherins

• Function: Cadherins are Ca2+-dependent proteins involved in cell adhesion.

• Types:

  • E-cadherin: Epithelial cells, stationary, present in adherens junctions.

  • N-cadherin: Neural cells, more migratory, found in adherens junctions.

• Role in Cancer: Regulate cell adhesion, influencing density and behavior; mutations in cadherins can promote tumor progression.

Cell Signaling Overview

• Types of Signals:

  • Hormones: Long-range signals affecting distant cells (endocrine signaling).

  • Growth Factors: Short-range signals acting on nearby cells (paracrine signaling).

Signaling Molecule Properties

• Lipid-Soluble Signals: Can cross the plasma membrane (e.g., steroid hormones).

• Lipid-Insoluble Signals: Require membrane receptors to transmit signals (e.g., insulin, epinephrine).

Steps of Cell Signaling

1. Signal Reception: Recognition of signaling molecule.

2. Signal Processing: Transduction and amplification of the signal.

3. Signal Response: Biological response by the cell.

4. Signal Deactivation: Mechanisms to turn off the signaling pathway.

Signal Receptors

• Types: Specific to their ligands, can be intracellular or membrane-bound.

• Dynamics: Numbers of receptors can change, offering regulation opportunities.

Lipid Soluble vs. Lipid Insoluble Signaling

• Lipid Soluble (Direct Signaling):

  • Diffuse through membranes.

  • Bind to receptors inside the cytosol, resulting in direct gene expression changes.

• Lipid Insoluble (Indirect Signaling):

  • Bind to membrane receptors, leading to shape changes that activate secondary messengers.

G Protein-Coupled Receptors (GPCRs)

• Structure: Transmembrane proteins with seven segments; connect to G-proteins inside the cell.

• Activation Steps:

  1. Inactive G-protein (GDP bound) activated by GTP.

  2. Active G-protein activates an enzyme, generating a second messenger (e.g., cAMP).

Second Messengers and Their Roles

• Types:

  • cAMP, cGMP, IP3, DAG, Ca2+ ions; facilitate signal transduction and cellular response.

• e.g.: cAMP activates Protein Kinase A leading to transcription changes in cells.

Enzyme-Linked Receptors

• Function: Transmembrane proteins that directly catalyze reactions in response to signals.

  • Example: Receptor Tyrosine Kinases (RTKs) that initiate phosphorylation cascades for signal propagation.

Ultimate Signal Responses

1. Activation or deactivation of existing proteins (short-term).

2. Changes in gene expression (long-term).

Signal Deactivation Mechanisms

• Important for terminating responses:

  • Hydrolysis of GTP to GDP on G-proteins.

  • Conversion of cAMP and cGMP to inactive forms by phosphodiesterase.

  • Re-sequestration of Ca2+ by the smooth ER.

Consequences of Dysregulated Signaling

• Receptors that are persistently active due to mutations can lead to diseases (e.g., cancer).

• Examples of mutations impacting signaling pathways, notably in GPCRs, have been identified in various diseases.

Interactions between Signal Pathways

• Crosstalk among pathways integrates varying signals, affecting the cellular response.

• Parallel Pathways: Multiple pathways can converge on similar intracellular targets, activating cascades that lead to cellular responses.