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Cell surface receptors and signalling molecules
- 1. BY C V ANURADHA I YEAR M.SC. HUMAN GENETICS Cell Surface Receptors, Signalling Molecules and G- protien couple receptors
- 2. Content Introduction to signalling Modes Adhesion Cell – cell interaction Cell to extracellular matrix Signalling molecules Types Functions Cell surface receptors Introduction Structure Functions G-Protien couple receptors
- 3. Introduction to cell signalling Cell signalling Complex system of communication Cellular activities Cell functions are coordinated Main components involved: Signalling molecules Receptors
- 4. Cell surface receptors Specialized proteins In plasma membrane Integral proteins Help in communication
- 5. Signalling molecules Chemicals and other molecules Act as ligands Bind to receptor Vary in size, shape and structure Some are capable of carrying signal over large distances
- 6. What are the possible responses? Differentiation Proliferation Survival Cell specific responses
- 7. Modes of signalling Intracrine Any hormone or ligand acting inside a cell For example if they act through nuclear receptors.
- 8. Modes of signalling Autocrine signalling Signal is to the same cell. Signalling is by binding with a cell surface receptor. Not a nuclear receptor.
- 9. Juxtacrine signalling Also known as contacct dependant signalling. Proximity between cells is mandatory for signalling to take place.
- 10. Paracrine signalling Cell to cell interaction Signal is produced for adjacent cells Ex: neurotransmitters in neurons
- 11. Endocrine signalling For hormone For signals that need to travel over distances Signals are carried by the blood stream Reaches target cell with receptors
- 13. Adhesion Adhesion is the property of cells to remain in contact with each other. Almost all cells of a tissue show this property. Such cells which are in close contact with each other for a long time form long lasting connections. Connections are called cell junctions. Nature of connection depends on the tissue type.
- 14. Cell – Cell interactions Three types based on the functions: Tight junctions Anchoring junctions Communicating junctions
- 15. Tight Junctions Called occluding junctions. Connect the plasma membranes of adjacent cells. Prevent leakage of small molecules from between them.
- 17. Anchoring junctions mechanically attach the cytoskeleton of a cell to the cytoskeletons of other cells to the extracellular matrix. Usually muscles and skin epithelium form such junctions. They can withstand some mechanical stress.
- 18. Desmosomes connect the cytoskeletons of adjacent cells. hemidesmosomes anchor epithelial cells to a basement membrane. Proteins called cadherins form these links.
- 19. Communicating junctions Cells communicate with adjacent cells through direct connections, called communicating junctions. Direct physical contact is established. Allows small molecules to pass.
- 20. Gap junctions Communicating junctions called gap junctions are composed of structures called connexons, complexes of six identical transmembrane proteins. Allows passage of larger molecules like sugar and amino acids. They are also regulated by hydrogen and calcium ions.
- 21. Cell – matrix interactions Anchoring junctions called adherens junctions are another type of junction that connects the actin filaments of one cell with those of neighboring cells or with the extracellular matrix. Its mediated by a protien called integrin.
- 22. Classification of cell junctions
- 23. Based on localization between cells
- 25. Cell – Matrix Adhesions: Hemidesmosomes A structure that joins a cell to its basal membrane rather than to another cell. The basal lamina is a layer of extracellular matrix secreted by the epithelial cells. Cytosolic plectin plate, integrin and lamins help in the formation.
- 26. Cell junctions based on functions
- 27. Adhesion by Cadherins and Integrins
- 29. Cadherins
- 30. Connexin Gap junction proteins Transmembrane proteins
- 31. Homophilic Heterophilic When same kind of receptors bind from 2 cells to form the junction. When different kind of receptors bind from 2 cells to form the junction. Classes of adhesion molecules
- 33. Mucins Selectins Mucins are a group of serine and threonine rich proteins and they are heavily glycosylated. i. Two mucin-like molecules (CD34 and GlyCAM-1) on certain endothelial cells of lymph nodes bind to L- selectin on leukocytes. ii. PSGL-1 is a mucin-like molecule on neutrophils. It interacts with E-selectin and P- selectin on inflammed vascular endothelium. Selectin CAMs are responsible for the initial stickiness of leukocytes to vascular endothelial cells. Glycoproteins that bind to specific carbohydrate groups. three molecules called L-selectin, E-selectin, and P-selectin. i. L-selectins are expressed by most leukocytes. ii. E-selectin and P-selectin molecules are expressed by vascular endothelial cells.
- 35. Signalling Molecules Messengers of cells For communication They can be compounds like peptides, amino acids, steroids or even gases. Secreted by signalling cell. Carried out by exocytosis while some by simple diffusion.
- 36. Types NO gas Steroids Neurotransmitters Peptide hormones and growth factors Second messengers
- 37. NO: Nitric oxide Major paracrine signalling molecule. In nervous system, immune system and circulatory systems. Diffuses easily across plasma membrane. It ultimately alters the activity of intracellular target enzyme. NO has a very short half life. Its toxic. Therefore, it functions over short distances. Induces relaxation and vaso dilation.
- 40. NO NO is also helps macrophages and neutrophils to kill microorganisms. CO, carbon monoxide is also used as a signal. It acts same as NO i.e, by stimulating guanylyl cyclase. It’s a neurotransmitter.
- 41. Steroids Small hydrophobic molecules. Act as hormones. Easily cross the membrane Aldosterone – regulates blood pressure Cortisol – Acts as a immunosuppressant
- 43. Neurotransmitters Carry signals between neurons i.e., between synapses. Diverse group of hydrophilic molecules. Hence the are unable to cross the plasma membrane and bind to receptors. Examples: Acetylcholine – connects motor nerves to muscles. Histamine – used in CNS Adrenaline – sleep, fight or flight responses, alertness
- 45. Peptide hormones and growth factors Widest range of signalling molecules in animals. Size can range from few to a hundred amino acids. They include peptide hormones, neuropeptides and growth factors. Peptide hormones: Insulin: regulates uptake of glucose and stimulates cell proliferation. Glucagon: Stimulates glucose synthesis. FSH (Follicle Stimulating Hormone): Stimulates growth of oocytes Prolactin: Stimulates milk production.
- 46. Neuropeptides function as neurotransmitters as well as neurohormones. Examples: Enkephalins and endorphins They both have analgesic properties. Decrease pain in CNS. They bind to the same receptors as morphine in the brain cells. Oxytocin – Smooth muscle contraction Vasopressin – stimulates water reabsorbtion
- 47. Polypeptide growth factors are signalling molecules that control growth and differentiation of cells. NGF (Nerve growth factor) – differentiation and survival of neurons. Epidermal growth factor – proliferation of different types of cells. Interleukin 2 – Proliferation of T lymphocytes.
- 48. Second Messengers Second messengers are Substances apart from the signalling molecules Used to relay the message Usually used to amplify the signal. Released and broken down by specific enzyme reactions Localised action Some examples are: cAMP – cyclic adenosine monophosphate cGMP – cyclic guanosine monophosphate IP3 – inositol triphosphate DAG – diacyl glycerol Ca2+ - Calcium ions
- 49. Identify the second messengers
- 50. Cell surface receptors Stuctures on the plasma membrane Each one has unique way of reacting to different molecules to perform functions.
- 51. Forms of receptors Steroid receptor G protein coupled receptors Tyrosine kinase receptors Cytokine superfamily receptor
- 52. Steroid receptors Found in cytosol, plasma membrane and the nucleas. Usually have nuclear receptors. Lead to change in gene expression causing alteration in the transcriptional activity. Some receptors are always bound to the DNA even when the hormone is not present. Eg: Thyroid hormone receptor. Some can bind only when the hormone is there. Eg: Estrogen and glucocorticoid receptors.
- 53. Many G protien receptors and ion gated receptors also act as steroid receptors. Structure: Variable domain: the structural component of the receptor DNA binding region: This region controls the gene to be activated. Hinge region: Controls movement of receptor Hormone binding domain: the region where the hormone or ligand binds.
- 55. HDAC Histone deacetylases (HDAC) are enzymes that remove acetyl groups (O=C-CH3) from a histone. allows the histones to wrap the DNA more tightly. DNA expression is regulated by acetylation and de- acetylation. Its action is opposite to that of histone acetyltransferase (HAT).
- 56. HAT Histone acetyltransferases (HAT) are enzymes that acytylate histone protiens by transferring a acetyl group from acetyl CoA. DNA is wrapped around histones. Therefore, by transferring an acetyl group to the histones, genes can be turned on and off. In general, histone acetylation increases gene expression.
- 58. Tyrosine kinase receptors It’s the largest group of enzyme linked receptors. Have receptors for most polypeptide growth factors. Act by phosphorylating the substrate protien. Plays major role in growth and differentiation. Include receptors for EGF, NGF, PDGF, insulin, and many other growth factors.
- 61. Cytokine Receptors called the cytokine receptor superfamily. includes the receptors for most cytokines like interleukin2 and erythropoietin and for some polypeptide hormones (growth hormone) Associated with non-receptor protein kinases (protein tyrosine kinases) which get activated on ligand binding.
- 63. G – Protein coupled receptors Known as 7TM receptor or seven transmembrane domain receptors. They pass through the plasma membrane 7 times forming many extracellular loops They have highly conserved cysteine residues forming disulfide bonds for stability. They extracellular regions may be glycosylated. The also have trimeric protiens: α, β and γ protiens which dissociate during the activation of the receptor.
- 64. Structure of G – protein linked receptors
- 65. Classification
- 66. Mechanism
- 68. The main response mechanism is by forming cAMP. But there are 2 pathways: cAMP signalling pathway PIP pathway
- 69. cAMP pathway
- 73. Desensitization Three general ways Inactivation They can become altered so they can no longer interact with G proteins. Sequestration They can be temporarily moved to the interior of the cell (internalized) so that they no longer have access to their ligand Downregulation They can be destroyed in lysosomes after internalization.
- 74. Rhodopsin like receptors Rhodopsin is a seven pass transmembrane molecule. Homologous to G protein coupled receptors. Activating signal is not a molecule, but a photon of light. This is usually active in olfactory and visual responses. Also acts as a neurotransmittors.
- 77. References https://en.wikipedia.org/wiki/Cell_surface_receptor https://www.boundless.com/biology/textbooks/boundle https://en.wikipedia.org/wiki/G_protein%E2%80%93c http://www.ncbi.nlm.nih.gov/books/NBK9866/ The Cell: A Molecular Approach. 2nd edition by Cooper and Sunderland
- 78. https://moodle.kent.ac.uk/external/mod/book/view .php?id=2396&chapterid=79 http://bpsbioscience.com/cell-surface-receptors http://www.scq.ubc.ca/cell-surface-receptors-a- biological-conduit-for-information-transfer/ https://www.glowm.com/section_view/heading/Cel l%2520Membrane%2520Receptors/item/281 : Cell membrane receptors by C V Rao and Carolyn M Klinge http://arbl.cvmbs.colostate.edu/hbooks/pathphys/e ndocrine/moaction/surface.html
- 80. Cell adhesion and CAMs http://www.cryst.bbk.ac.uk/pps97/assignments/projects/emil ia/Adh_mol.HTM https://www.rndsystems.com/resources/articles/adhesion- molecules-ii