8) Cell adhesion and the ECM
Cards (11)
- Cell-ECM interactions are regulated by matrix receptors
- Matrix receptors have three major domains:
- Extracellular domain: Interacts with ligands in the ECM
- Transmembrane domain: anchors receptors to the cell membrane
- Intracellular domain: Links to the cytoskeleton, allowing receptors to transmit signals from extracellular cues
- Integrin Summary:
- Structure: Transmembrane protein dimer made up of 18 α and 8 β subunits (creating 24 different combinations of integrins)
- Extracellular domain binds to ECM proteins
- Intracellular domain binds to adaptor proteins, indirectly linking them to the cytoskeleton
- Function: Act as a bridge for the ECM and cytoskeleton
- Cell-matrix anchoring junctions link the ECM to the Cytoskeleton, facilitating cellular movement and maintaining tissue integrity
- Types of cell-matrix anchoring junctions:
- Actin-linked Junctions
- Hemidesmosomes
- Actin-Linked Junctions:
- Structure: Integrins link to the ’Actin cytoskeleton’.
- Integrins have a extracelluar domain (binds to the ECM) and an intracellular domain (binds to actin filaments inside the cell via adaptor proteins)
- Hemidesmosomes summary:Structure: Cell Junctions that link epithelial cells to the basal lamina
- Integrins active and inactive states summary:
- Integrins have active states: form attachments
- inactive states: dont form attachments
⤷ This allows cells to migrate through and attach to the ECM - outside-in-signalling:
- extracellular signals (such as binding to ECM proteins) cause conformational changes in integrin structure
- This activates integrins, leading to increased affinity for ECM ligands
- Inside-out signalling Summary:
- Growth factors/intracellular signals. stimulate adaptor proteins to bind to an integrin
- ⤷ This causes a confirmational change, activating it.
- Downstream Signalling:When Integrins form attachments, they activate intracellular signalling pathways such as:
- Survival
- Proliferation
- Motility