Cell Adhesion and Extracellular Matrix PDF

Cell Adhesion Name: Amy Bradshaw Office: STB 325 Email: [email protected] Phone: 792-4959 OUTLINE: Cell Adhesion Aka How our Cells Stay Connected I). Introduction: Epithelial Tissue versus Connective Tissue II). Cell Junctions A) Occluding or Tight Junctions 1) Barrier Function 2) Claudins and occl...

Cell Adhesion Name: Amy Bradshaw Office: STB 325 Email: [email protected] Phone: 792-4959 OUTLINE: Cell Adhesion Aka How our Cells Stay Connected I). Introduction: Epithelial Tissue versus Connective Tissue II). Cell Junctions A) Occluding or Tight Junctions 1) Barrier Function 2) Claudins and occludins B) Communicating Junctions 1) Gap Junctions a) Connexin proteins: connexon channels C) Anchoring Junctions: 1) Cadherin Family: Cell:Cell Interaction. a) Adherens Junctions b) Desmosomes 2) Integrin Family: Extracellular Matrix a) Hemidesmosomes b) Focal Adhesions III). Cell-Cell Adhesion A) CAM: Cell Adhesion Molecules 1) Cadherins 2) IgG Superfamily a) N-CAM: Neural cell adhesion molecule 3) Selectins a) Selectins in inflammatory cell recruitment 7/25/2022 COM Block 1 Cell:Cell Adhesion and Cell Adhesion to the Extracellular Matrix Amy Bradshaw [email protected] Images from Medical Cell Biology, Goodman Molecular Biology of the Cell, Alberts Tissue Organization Involves Cell:Cell Interaction and Cell:Extracellular Matrix Interaction Epithelial cells bind to each other and to ECM proteins in the Basement membrane through specialized cell surface receptors. Epithelial cells have multiple cell:cell contacts and also cell:ECM interaction. 1 7/25/2022 Cell Junctions Elaborate subcellular structures that are visible by electron microscopy. Each type of junction has specific cellular functions. Each type of junction has its own distinct protein composition. Tight junctions, Gap junctions, and Anchoring junctions are three examples of Cell junctions. Cell Junctions were first identified as electron dense structures when viewed by electron microscopy Plasma membrane Cell junctions Plasma membrane Two adjacent epithelial cells in a mollusk. 2 7/25/2022 Tight Junctions or Occluding Junctions: Contribute to the Barrier Function of Epithelial Cell Layers: Separate fluids on either side with different chemical compositions. Example: Gut Epithelia – glucose is actively transported from the lumen of the gut through Na+‐driven symports. The glucose then moves through the cells and diffuses out through glucose carriers in the baso‐lateral membrane to enter the bloodstream. 3 7/25/2022 Claudins and Occludins: transmembrane proteins that compose Tight Junctions. Claudin/occludin on one epithelial cell binds to claudin/occludin proteins on neighboring cells to form a tight seal. Extracellular space Sealing strand of tight junction proteins Gap Junctions mediate cell‐cell communication Cross-section En-face 4 7/25/2022 Gap Junctions allow small molecules to pass from one cell to another Gap Junctions are composed of proteins called connexins that come together to form channels called connexons. Neighboring cells express connexons on their cell surface, these connexons bind to connexons on adjacent cells to form a intercellular channel. 5 7/25/2022 Anchoring Junctions: Structures associated with the plasma membrane that provide structural anchors in the flimsy lipid bilayer of the plasma membrane and allow force generation between cells or between cells and the extracellular matrix. Anchoring junctions are a broader category than tight and gap junctions because they can mediate both cell:cell and cell: ECM interactions. Anchoring Junctions are prominent in tissue under mechanical stress such as skeletal/heart muscle and skin. 6 7/25/2022 General Structure of Anchoring Junctions: 1) Plasma membrane receptor with an extracellular domain, a membrane spanning domain, and a cytoplasmic tail (green), 2) anchoring proteins that bind to the cytoplasmic tail of the receptors and cytoskeletal elements (blue), and 3) cytoskeleton (red). Types of Anchoring Junctions Cell:cell(2) Cell:ECM(2) Adherens Junctions: Cell to cell contacts that link to the actin cytoskeleton. Desmosomes: Cell to cell contacts that link to intermediate filaments. Hemidesmosomes: Cell to ECM contacts that link to intermediate filaments. Focal Adhesions: Cell to ECM contacts that link to the actin cytoskeleton. 7 7/25/2022 Anchoring Junctions (Mature Focal Adhesion) Anchoring Junctions Adherens Junctions function in cell:cell interactions and link to the actin cytoskeleton Cells are able to connect their actin cytoskeleton through adherens junctions so that force can be transmitted throughout an epithelial sheet. 8 7/25/2022 Anchoring Junctions Cadherins are the transmembrane receptor proteins in Adherens junctions. Cadherin receptors are Ca2+ ‐ dependent. Anchoring Junctions Adherens Junctions (or adhesion belts): allow the cells to connect cytoskeletal elements in neighboring cells to drive morphogenic processes critical for development. 9 7/25/2022 Anchoring Junctions Desmosomes occur between adjacent cells. Desmosomes form button‐like rivets at the cell membrane. Cadherin family members are cell surface receptors that interact with anchoring proteins that connect to intermediate filaments. Anchoring Junctions Desmosomes from Rat Intestines Joining 2 Epithelial Cells Plasma membrane Intermediate filaments Anchoring proteins Cadherin family receptors 10 7/25/2022 Anchoring Junctions also occur between cells and the Extracellular Matrix. Integrin receptors bind cells to extracellular matrix: Heterodimers composed of one  subunit and one  subunit Anchoring Junctions Integrins can be in an inactive state on the cell surface and become activated (able to bind ECM ligands) by intracellular signaling molecules Integrins are the cell surface receptors used in both hemidesmosomes and focal adhesions 11 7/25/2022 Anchoring Junctions Hemidesmosomes form between cells and the extracellular matrix. Integrin receptors connect via anchor proteins to intermediate filaments. Anchoring Junctions Hemidesmosomes are critically important in anchoring the epidermis to the dermis, for example. Not used for cell movement. These structures are holding cells in place. Mutations in critical proteins that compose hemidesmosomes give rise to severe blistering disorders. 12 7/25/2022 Anchoring Junctions Hemidesmosomes in skin: Epidermal epithelial cells bind to basement membrane to anchor the epidermis to underlying dermal connective tissue. Hemidesmosome Basement Membrane Dermal collagen fibrils Anchoring Junctions Focal Adhesions occur between cells and extracellular matrix. Integrins bind to ECM components and link to actin cytoskeleton via anchoring proteins Yellow: Integrin receptors Red: anchor proteins Green: actin cytoskeleton Focal Adhesions can be used for cell movement 13 7/25/2022 Anchoring Junctions Focal Adhesions occur between cells and extracellular matrix. Integrins bind to ECM components and link to actin cytoskeleton via anchoring proteins Yellow: Integrin receptors Red: anchor proteins Green: actin cytoskeleton Focal Adhesions can be used for cell movement Summary of Cell Junctions 14 7/25/2022 Cell Adhesion Cell adhesion precedes the formation of cell junctions. Cells need to first establish whether they would like to form a cell junction by sensing cell surface signals through cell adhesion. Cell adhesion receptors can bind using two distinct mechanisms: 1) Homophilic binding 2) Heterophilic binding Cell adhesion does not necessarily lead to the formation of a cell junction. Complexes that form during initial cell adhesion events are not as protein dense as those of cell junctions and are not visible by electron microscopy, for example. Cell Adhesion Differential expression and recognition by cell surface adhesion molecules allows for and directs cell sorting mechanisms in tissues. 15 7/25/2022 Examples of different classes of Cell Adhesion Receptors Initiation of a Cell Adhesion Event Tension created by cell attachment through cell surface receptors leads to unfolding of cytoplasmic proteins bound to these receptors, such as ‐ catenin, exposing sites on ‐catenin. The exposed sites are now able to interact with other cytoplasmic proteins and cytoskeletal elements. 16 7/25/2022 Maturation of Cell Adhesion Interaction to an Adherens Junction Example of a Cell Adhesion Event: Selectins contribute to inflammatory cell recruitment to sites of injury 1) A white blood cell in the circulation makes contact with endothelial cells as they bounce through the blood stream. Quiescent endothelial cells do not express cell surface receptors that bind to white blood cells so they don’t linger on blood vessel walls. 2) “Activated endothelium” initiate expression of selectins that form a weak adhesion event with white blood cells that tether the white blood cells to the surface of the blood vessel. 3) Further activation of endothelial cells increases expression of stronger adhesion receptors, integrins. Integrin adhesion signals the white blood cells to bind and to intiate cell migration (extravasation) into the underlying connective tissue. 17 7/25/2022 To Sum it All Up…………… (Mature Focal Adhesions) Laminin Collagen IV Nidogen HSPG:Perlecan Connective Tissue: Fibrillar collagen Proteoglycans 18