Junctions-RSK-Lecture5-6.pdf

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(1)M. Sc. Botany / Zoology / Microbiology SEMESTER - I COURSE – 101. CELL BIOLOGY UNIT - 3. LECTURES :. Cell Adhesion & Junctions Between Cells DR. RAHUL KUNDU Associate Professor DEPARTMENT OF BIOSCIENCES SAURASHTRA UNIVERSITY RAJKOT.

(2) Cell Adhesion • Structural Integrity • External Sensing • Migration • Regulation of Transport • Communication Why Adhesion? • Adhesion refers to “stickiness” • Evolution of multicellular organisms developed specialized cells and tissues • Embryonic development also allows differentiation of different cell/tissue types • Interaction between cell-cell and cell-extracellular matrix by specific contacts • Cell Biology definition different from Clinical term • Clinical term “adhesions” bands of scar-like tissue forming between two surfaces inside the body.

(3) Adhesive Functions . Basal lamina assemble and organize epithelia. . Smooth muscle o. Maintains integrity during contraction. . Binds growth factors. . Neurons growth cone guidance, fasiculation. . Cell Migration. . Development - migration, cell sorting, tissue development. • Transmigration, wound healing, macrophages.

(4) Cell adhesion Molecules and their Characteristics FAMILY integrins. selectins. Ig superfamily (immunoglobulin) cadherens. LOCATION AND/OR FUNCTION Focal adhesions, Hemi Desmosomes Leukocyte (Spreading) Adhesion, Primarily cell matrix adhesion but also in some cell-cell adhisions. circulating cells and endothelial cells, "rolling" adhes ion important in immune response. LIGANDS RECOGNIZED (E) fibronectin, collagen, laminin, immunoglobulins, (I) actin filaments. COMMENTS. carbohydrates. require Ca2+. adherens junctions, desmosomes. (E) homophillic, (I) actin filaments, termediate filaments. relatively low affinities -6(KD~ 10 10-8 mol/liter). integrins, homophillic require Ca2+.

(5) Overview of the types of molecules that bind cells to each other and to the extracellular matrix.

(6) Types of Adhesion Molecules. . Cadherins. . Immunoglobulin Superfamily. . Selectins. . Gap Junctions. • Integrins.

(7) Cadherins . vertebrates have 20+, separate gene loci. . E-cadherins (epithelial cells). . N-cadherins (nerve and muscle). . P-cadherins (placenta and epithelial). . Contain 5 cadherin repeats. . Each comprising sandwich of beta sheets. . requires calcium ions to bind. . Homophilic binding through end element o. Like Functional unit of a dimer.

(8) . Immunoglobulin Superfamily Vertebrates have 100+. . In addition to adhesion they also have role in immune system. . Contain varying number of Ig-related domains. . Comprising sandwich of beta sheets. • Held together by hydrophobic interactions.

(9) Selectins. . Vertebrates have only in circulatory system. . Role in adhesion of leukocytes (blood cells) to endothelium (vessel wall). . Cooperate with integrins and Ig-SF receptors. . Selectins 2 Heterophilic interactions. . Bind counterreceptors. . Glycosylated proteins. Bind through C terminal lectin domain of selectin.

(10) Integrins. . Mammals have genes for 18 alpha and eight beta integrins. . Role in cell adhesion to extracellular matrix (ECM) basement membranes. . Induction of cell polarization by adhesion. . Mainly receptors for ECM proteins. . Fibronectin, laminin, collagen. . Some heterotypic binding Ig superfamily. . Interact with cell cytoskeleton signalling.

(11) Adhesion complexes Junction type. Function. Extracellular or adjacent cell attachment. Intracellular attachment. Tight junction. regulate transport between cells and along cell membrane. Adherens. structural, cell-cell or cellmatrix. Gap junctions. cell-cell communication via ion channels formed by and small molecule exchange connexin subunits. Desmosome. structural, cell-cell. cadherin. intermediate filaments. Hemidesmosome. structural, cell-matrix. basal lamina via integrins. intermediate filaments. Focal adhesions. structural, cell-matrix. ECM proteins via integrins. actin filaments. ECM proteins or cadherins actin in adjacent cell filaments.

(12) Tight Junction. seals neighbouring cells. Adherens Junction. joins actin bundles between cells. Desmosome. joins intermediate filaments between cells. Gap Junction. cell-cell communication, passage of small molecules. anchors cell intermediate filaments to to basal Hiemidesmosome lamina (extracellular matrix).

(13) Junctions Between Cells In many animal tissues (e.g., connective tissue), each cell is separated from the next by an extracellular coating or matrix. However, in some tissues (e.g., epithelia), the plasma membranes of adjacent cells are pressed together. Four kinds of junctions occur in vertebrates: Tight junctions Adherens junctions Gap junctions Desmosomes In many plant tissues, it turns out that the plasma membrane of each cell is continuous with that of the adjacent cells. The membranes contact each other through openings in the cell wall called Plasmodesmata..

(14) Tight Junctions •. Epithelia are sheets of cells that provide the interface between masses of cells and a cavity or space (a lumen). • The portion of the cell exposed to the lumen is called its apical surface. • The rest of the cell (i.e., its sides and base) make up the basolateral surface. • Tight junctions seal adjacent epithelial cells in a narrow band just beneath their apical surface.. Tight junctions perform two vital functions: • They prevent the passage of molecules and ions through the space between cells. So materials must actually enter the cells (by diffusion or active transport) in order to pass through the tissue. This pathway provides control over what substances are allowed through. • They block the movement of integral membrane proteins (red and green ovals) between the apical and basolateral surfaces of the cell. Thus the special functions of each surface, for example • receptor-mediated endocytosis at the apical surface • exocytosis at the basolateral surface can be preserved..

(15) Adherens Junctions • Adherens junctions provide strong mechanical attachments between adjacent cells. They hold cardiac muscle cells tightly together as the heart expands and contracts. • They hold epithelial cells together. • They seem to be responsible for contact inhibition. • Some adherens junctions are present in narrow bands connecting adjacent cells. • Others are present in discrete patches holding the cells together..

(16) Adherens junctions are built from: cadherins - transmembrane proteins (shown in red) whose extracellular segments bind to each other and whose intracellular segments bind to catenins (yellow). Catenins are connected to actin microfilaments One of the oncogenes that is frequently found in colon cancer appears to be the mutated version of a protein that normally interacts with catenins. Loss of functioning adherens junctions may also lead to tumor metastasis..

(17) Gap Junctions •. • •. •. • • •. Gap junctions are intercellular channels some 1.5 - 2 nm in diameter. These permit the free passage between the cells of ions and small molecules (up to a molecular weight of about 1000 daltons). They are constructed from 4 (sometimes 6) copies of one of a family of a transmembrane proteins called connexins. Because ions can flow through them, gap junctions permit changes in membrane potential to pass from cell to cell. Examples: The action potential in heart (cardiac) muscle flows from cell to cell through the heart providing the rhythmic contraction of the heartbeat. At the few electrical synapses in the brain, gap junctions permit the arrival of an action potential at the synaptic terminals to be transmitted to the postsynaptic cell without the delay needed for release of a neurotransmitter. As the time of birth approaches, gap junctions between the smooth muscle cells of the uterus enable coordinated, powerful contractions to begin. Several inherited disorders of humans such as certain congenital heart defects and one form of congenital deafness have been found to be caused by mutant genes encoding connexins..

(18) Desmosomes Desmosomes are localized patches that hold two cells tightly together. They are common in epithelia (e.g., the skin). Desmosomes are associated with intermediate filaments in the cytoplasm. Carcinomas are cancers of epithelia. However, the cells of carcinomas no longer have desmosomes. This may account for their ability to metastasize..

(19) Plasmodesmata Although each plant cell is encased in a boxlike cell wall, it turns out that communication between cells is just as easy, if not easier, than between animal cells. Fine strands of cytoplasm, called plasmodesmata, extend through pores in the cell wall connecting the cytoplasm of each cell with that of its neighbors. Plasmodesmata provide an easy route for the movement of ions, small molecules like sugars and amino acids, and even macromolecules like RNA between cells. A report in the 6 March 1998 issue of Science (Jorgensen et al., p. 1486) describes how plasmodesmata enable plants to transmit signals - such as the need to mount a defense against a viral infection - from one part of the plant to another. Plasmodesmata are sheathed by a plasma membrane that is simply an extension of the plasma membrane of the adjoining cells. This raises the intriguing question of whether a plant tissue is really made up of separate cells or is, instead, a syncytium: a single, multinucleated cell distributed throughout hundreds of tiny compartments!.

(20) Abnormalities Desmosomes pemphigus and bullous impetigo- antibodies made against one of their own desmosomal cadherin proteins antibodies bind to and disrupt the desmosomes that hold together skin epithelial cells severe skin blistering, leakage of body fluids palmoplantar keratoderma Arrhythmogenic right-ventricular cardiomyopathy (ARVC) Oncogenesis not the cause but transformed cells loose adhesion, able to "break away" and spread (metastisis)..

(21) THAT’S ALL ABOUT. JUNCTIONS BETWEEN CELLS. THANKS.

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