Cell Connections & Junctions by Dr. Vani Gupta

1. Cell Connections & Junctions by Dr. Vani Gupta

2. Definition and Classification of cell junction Cell junction is the connection between the neighbouring cells or the contact between the cell and extracellular matrix. It is also called membrane junction. Cell junction are classified into three types a-Occluding junction b-Communicating junction c-Anchoring junction.

3. Cell Adhesion Molecules (CAMs) Important cell surface proteins molecules promoting cell–cell and cell–matrix interactions. Important for many normal biological processes -embryonic cell migration, immune system functions, wound healing. Involved in intracellular signaling pathways (primarily for cell death/survival, secretion etc.)

4. Cell Adhesion Molecules (CAMs) • Express 3 major domains: • The extracellular domain allows one CAM to bind to another on an adjacent cell. • The transmembrane domain links the CAM to the plasma membrane through hydrophobic forces. • The cytoplasmic domain is directly connected to the cytoskeleton by linker proteins.

5. Cell Adhesion Molecules (CAMs) Binding of an adhesion molecule on one cell to the same adhesion molecule on a second cell Cadherin - cadherin An adhesion molecule on one cell type binds to a different type of cell adhesion molecule on a second cell Selectins – mucins The linker molecule in most cases is Laminin, a family of large cross shaped molecules with multiple receptor domains. Interactions between CAMs can be mediated by :

6. These cell adhesion molecules can be divided into 4 major families • The cadherin superfamily • The selectins • The immunoglobulin superfamily and • The integrins

7. The Cadherin superfamily • Cadherins are the most prevalent CAMs in vertebrates. • 125 kD transmembrane glycoproteins - mediate intercellular adhesion in epithelial and endothelial cells by Ca2+ dependent homophilic adhesion. • Primarily link epithelial and muscle cells to their neighbors • Form desmosomes and adherens junctions • Play critical role during development (cell sorting). • Do not interact with extracellular matrix.

8. The Cadherin superfamily Contain a short transmembrane domain and a relatively long extracellular domain containing four cadherin repeats (EC1-EC4), each of which contains calcium binding sequences Cadherins interact with specific cytoplasmic proteins, e.g., catenins (α, β and γ), as a means of being linked to the actin cytoskeleton. The binding of cadherins to the catenins is crucial for cadherin function.

9. The Selectins • Structural features of selectins include: • NH2-terminal C-type Ca2+ dependent lectin like binding domain, which determines the ability of each selectin to bind to specific carbohydrate lingands. • an epidermal growth factor-like region. • a number of repeat sequences. • a membrane-spanning region and • a short cytoplasmic region

10. Immunoglobulin Superfamily Molecules • Consists of more than 25 molecules. • Important ones being: • Intracellular adhesion molecule 1(ICAM1; CD54) • Intercellular adhesion molecule 2 (ICAM2), • Vascular cell adhesion molecule1 (VCAM1; CD106), • Platelet endothelial cell adhesion molecule 1 (PECAM 1; CD31) and • the mucosal addressin cell adhesion molecule 1 (MAdCAM1).

11. The integrins Fifteen different α and eight different β subunits give rise to over twently different heterodimeric combinations at cell surfaces. Bind epithelial and muscle cells to laminin in the basal lamina Allow platelets to stick to exposed collagen in a damaged blood vessel Allow fibroblasts and white blood cells to adhere to fibronectin and collagen as they move

12. Types of cell junction in animal tissue

13. Occluding Junction • A cell-cell junction that seals cells together in an epithelium in a way that prevents even small molecules from leaking from one side of the sheet to the other. • Tight Junction Tight Junction- occluding junctions / zonulae occludens - zonula occludens), are the closely associated areas of two cells whose  membranes join together forming a virtually impermeable barrier to fluid. • A type of junctional complex present only in vertebrates. • Consist of linear array of several integral proteins. • Junctional proteins occludins and claudins & members of IG suprfamily are transmembrane proteins.

14. Function of Tight Junction Strength and stability Selective permeable for ions. Fencing function Maintance of cell polarity Blood-brain barrier Cludin -16 in Thick Junctions of Ascending Loop of henle. Cludin- 15 Permability of cations / anions.

15. Adhering Junctions Desmosome- Connects intermediate filament of one cell with other cells. Claudin Hemidesmosome Desmoplakin is essential for normal desmosomal adhesion.

16. Communicating Junction Cell junction which permit the intercellular exchange of substance are called communicating junction, these junction permit the movement of ions and molecules from one cell to another cell. a- Gap junction b- Chemical synapse

17. Gap Junction Gap junctions are clusters of intercellular channels that allow direct diffusion of ions and small molecules between adjacent cells. At gap junctions, the intercellular space narrows from 25 nm to 3 nm. gap junctions were first discovered in myocardium and nerve because of their properties of electrical transmission between adjacent cells (Weidmann 1952; Furshpan and Potter 1957).

18. Low resistance intercellular junction that allows passage of ions and smaller molecules between the cells. • It present in heart, basal part of epithelial cell of intestinal mucosa, etc • Junctional unit-Connexons- 6 connexins • Connexon of one cell have allignment with connexon of other cells.

19. Gap Junction Electron microscopy of gap junctions joining adjacent hepatocytes in the mouse. The gap junction (GJ) is seen as an area of close plasma membrane apposition

20. Function of gap junction- • channel passage the substance have molecular weight less than 1000. • Exchange of chemical messenger between cells • Rapid propagation of action potential from one cell to another cell.

21. Desmosomes • Also known as macula adherens is a cell structure specialized for cell-to-cell adhesion. • Are molecular complexes of cell adhesion proteins and linking proteins that attach the cell surface adhesion proteins to intracellular keratin cytoskeletal filaments. • The cell adhesion proteins of the desmosome, desmoglein and desmocollin, are members of the cadherin family. • On the cytoplasmic side of the plasma membrane, there are two dense structures called the Outer Dense Plaque (ODP) and the Inner Dense Plaque (IDP). • The Outer Dense Plaque is where the cytoplasmic domains of the cadherins attach to desmoplakin via plakoglobin and plakophillin. • The Inner Dense Plaque is where desmoplakin attaches to the intermediate filaments of the cell.

22. Desmosomes

23. Hemidesmosomes Hemidesmosomes look like half-desmosomes that attach cells to the underlying basal lamina. Rather than using desmogleins, hemidesmosomes use desmopenetrin cell adhesion proteins,which are members of Integrin family. The integrin molecule attach to one of many multi-adhesive proteins such as laminin, resident within the extracellular matrix, thereby forming one of many potential adhesions between cell and matrix.

24. Chemical synapse Chemical synapse is the junction between a nerve fibre and a muscle fiber or between two nerve fibre ,through which signals transmitted by the release of chemical transmitter.

27. Anchoring junction. Anchoring junction are the junction ,which provides strength to the cell by acting like mechanical attachment. These junction provide firm structural attachment between two cells or between a cell and extracellular matrix Anchoring junction are responsible for structural integrity of the tissue.

28. various cell junctions found in a vertebrate epithelial cell, classified according to their primary functions

31. Q1-which of the following is a cell adhesion molecule a-integrin b-lysin c-myosin d-keratin

32. Q2-desmosomes differ from tight junction because a-allow molecules to pass in the intercellular space b-are non-communicating c-are present in plants d-lack proteins

33. Q3-the Cell Junctions allowing exchange of cytoplasmic molecules between two cells are called: A. Gap JunctionsB. Tight JunctionsC. Anchoring JunctionsD. Focal Junctions

34. 4- Desmosome has the following characters except: a- is a disk like attachment between cells b- is located only between epithelial cells c- is specialized for adhesion e-is called macula adherns

35. 5- Gap junctions a- permit the passage of large proteins from cell to cell b- form part of the classical junctional complex c- exist only between epithelial cells d- are areas of low resistance for nerve stimulation

36. Q-6 Which of the following apply to intercellular junctions? a) The three major adhesive junctions of animal cells are adherens junctions, desmosomes and hemidesmosomes. b) Desmosomes and hemidesmosomes connect epithelial cells to their basement membrane and adjacent cells respectively. c) Gap junctions and plasmodesmata are homologous structures. d) The junctional complexes of gastrointestinal enterocytes ensure that nutrients are only absorbed through the spaces between the cells, which prevents them absorbing potentially harmful substances. ANS-a

37. Q-7 tight junction a-are essential for metabolic coupling b-dont occur in vertebrates c-have the closest approach of two plasma membranes of any junction d-surround connexions

38. Q-8 hemi desmosome differs from spot desmosome because hemi desmosome a-connect cell to cell b-connect extracellular matrix to extracellular matrix c-connect cell to extracellular matrix d-having tonofilament ,made up of intermediate filament

39. Desmosomes are made-up of integral protein a. Integrein b. Connexin C. Selectin d. Claudin.

40. Hemidesmosomes are connections between Cell to cell Cell to internal organ Cell to matrix Cell to cell memberane