1. Dr Mahmood S Choudhery, PhD Assistant Professor Advance Center of Research in Biomedical Sciences Incharge Tissue Engineering Laboratory, Mayo Hospital Lahore, Pakistan King Edward Medical University, Lahore, Pakistan

2. Learning objective  How cells attach to neighboring cells  How cells communicate with other cells and extracellular matrix (ECM)  Types of different junctions  Role of ECM in cell signaling

3. They need to perform specific functions more effectively Permits the organism as a whole to move, metabolize, reproduce, and carry out other essential activities.

4. Integration of Cells into Tissues Involves 2 processes 1. Cell Recognition 2. Cell Adhesion

5. Cell Adhesion…………… 1. Cell-cell adhesion 2. Cell-matrix adhesion Adhesion Receptors Cells can adhere to each other by two ways Cell Adhesion Molecules (CAMs)

6. Cell Adhesion Molecules (CAMs)……….. 1. Are proteins (glycoproteins) 2. Involved in binding with other cells or with ECM 3. Typically transmembrane proteins 4. Cluster to form specialized cell junctions

7. Cell Adhesion Molecules……….. 4 Types Cadherins Immunoglobulins Integrins Selectins

8. TYPES OF INTERACTIONS Between adhesion molecules  Homophilic interactions  Heterophilic interactions Between cells  Homotypic interactions  Heterotypic interactions

9. What are Cis and Trans interactions?

10. SPECIALIZED CELL JUNCTIONS  Between cells Tight junctions Adhesive/ Anchoring junctions Gap junctions  Between cells and matrix Hemidesmosomes Focal Junctions

11. 2. Cell junctions - types based on function  Adhering junctions: 1. Tight junctions 2. Adhesive/ Anchoring junctions 3. Hemidesmosomes 4. Focal Junctions  Communicating junctions: 1. Gap junctions 11

12. 1. Tight Junctions  Only found in epithelial cells  Composed of 3 transmembrane protein families  Prevent substances from moving through intercellular spaces

13. 2 types a)Desmosomes b)Adherens Junctions 2. Adhesive/ Anchoring junctions  Hold cells tightly together  Connect a cell’s cytoskeleton to another cell

14. 1. Form links between cells 2. Connect intermediate filaments of adjacent cells 3. Composed of cadherins

16. Under the cell membrane, contractile fibers of microfilaments connect to cell membrane proteins called cadherins b) Adherens Junctions

17.  Homophilic pairing of E- cadherins  Adapter proteins (plakoglobin and α and βcatenins) link cadherins to the belt of actin filaments. 17

18. Gap junctions allow cells to exchange electrical and/or chemical signals Composed of proteins that form channels that allow small molecules to pass. Subunits of these channels are connexins that are assembled together to make connexons. The connexons from 2 cells join together to make a gap junction.

19. This channel is big enough to allow small molecules such as inorganic ions, and other small water soluble molecules (smaller than 1000kDa) to pass between the cells. However the channel is too small for proteins, nucleic acids or sugars to pass through.

20. Gap Junctions desmosome Gap Junctions: pairs of channels connect insides of adjacent cells Liver Plasma membrane (edge view) Liver cells Plasmodesmata Plasmodesmata connect insides of adjacent cells Plasma membrane (edge view) Root cells Cell wall (edge view) Middle lamella (edge view) Root AnimalsPlants

21.  Connections between cell and ECM  Composed of Integrins

24. What is ExtraCellular Matric (ECM)? Secreted by surrounding cells EXTRACELLULAR MATRIX

25. 1. Basal lamina 2. Interstitial Matrix Two types of Extracellular Matrix

26. ECM COMPONENTS 1.Proteoglycans 2.Structural Proteins (Collagens and Elastins) 3.Adhesive Glycoproteins (Fibronectins and Laminins)

28. 1.Proteoglycans: (Protein-polysaccharide complexes) ECM components……………. Composed of a core protein and GAGs Have net negative charge Trap and store growth factors

29. 2. Structural Glycoproteins (Collagens and Elastins) ECM components……………. 3. Adhesive Glycoproteins (Fibronectins and Laminins) Collagens are the main proteins of ECM Elastin give elasticity to tissues  Fibronectin connect cells with collagen fibers in the ECM and integrin receptors on cell membrane  Laminin found in the basal lamina

30. Role of Extracellular Matrix in Cell Signaling  Provides space where different ligands and growth factors are released  Act as a reservoir for various growth factors  Different proteins of ECM act as ligand for cell receptors

31. How Extracellular Matrix Components Mediate Cell Signaling? Integrins are transmembrane receptors for extracellular matrix (ECM) proteins such as collagens, fibronectin, laminins and vitronectin.

32. The Extracellular Matrix Participates in Signaling lntegrin adhesion receptor mediated signaling pathways that control diverse cell functions.

33. Recommended Books Molecular Cell Biology By Lodish 7 th Molecular Biology of The Cell by Bruce Alberts