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BY
C V ANURADHA
I YEAR
M.SC. HUMAN GENETICS
Cell Surface Receptors,
Signalling Molecules and G-
protien couple receptors
Content
Introduction to signalling
 Modes
Adhesion
 Cell – cell interaction
 Cell to extracellular matrix
Signalling...
Introduction to cell signalling
Cell signalling
 Complex system of communication
 Cellular activities
 Cell functions ...
Cell surface receptors
Specialized proteins
In plasma membrane
Integral proteins
Help in communication
Signalling molecules
Chemicals and other molecules
Act as ligands
Bind to receptor
Vary in size, shape and structure
...
What are the possible responses?
Differentiation
Proliferation
Survival
Cell specific responses
Modes of signalling
Intracrine
 Any hormone or ligand
acting inside a cell
 For example if they act
through nuclear
rec...
Modes of signalling
Autocrine signalling
 Signal is to the same
cell.
 Signalling is by binding
with a cell surface
rec...
Juxtacrine signalling
 Also known as contacct
dependant signalling.
 Proximity between cells
is mandatory for
signallin...
Paracrine signalling
 Cell to cell interaction
 Signal is produced for
adjacent cells
 Ex: neurotransmitters
in neurons
Endocrine signalling
 For hormone
 For signals that need to
travel over distances
 Signals are carried by the
blood st...
Adhesion
Adhesion is the property of cells to remain in contact
with each other.
Almost all cells of a tissue show this ...
Cell – Cell interactions
Three types based on the functions:
 Tight junctions
 Anchoring junctions
 Communicating junc...
Tight Junctions
Called occluding
junctions.
Connect the plasma
membranes of adjacent
cells.
Prevent leakage of small
mo...
Anchoring junctions
mechanically attach the
cytoskeleton of a cell
 to the cytoskeletons of
other cells
 to the extrace...
Desmosomes connect the cytoskeletons of adjacent
cells.
hemidesmosomes anchor epithelial cells to a
basement membrane.
...
Communicating junctions
Cells communicate with
adjacent cells through
direct connections, called
communicating junctions....
Gap junctions
Communicating junctions
called gap junctions are
composed of structures
called connexons, complexes
of six ...
Cell – matrix interactions
Anchoring junctions
called adherens
junctions are another
type of junction that
connects the a...
Classification of cell junctions
Based on localization between cells
Cell – Matrix Adhesions:
Hemidesmosomes
A structure that joins
a cell to its basal
membrane rather
than to another cell.
T...
Cell junctions based on functions
Adhesion by Cadherins and Integrins
Cadherin Integrin
Cadherins
Connexin
Gap junction proteins
Transmembrane proteins
Homophilic Heterophilic
When same kind of
receptors bind from 2
cells to form the
junction.
When different kind of
recep...
Mucins Selectins
 Mucins are a group of serine and
threonine rich proteins and they
are heavily glycosylated.
 i. Two mu...
Signalling Molecules
Messengers of cells
For communication
They can be compounds like peptides, amino acids,
steroids o...
Types
NO gas
Steroids
Neurotransmitters
Peptide hormones and growth factors
Second messengers
NO: Nitric oxide
Major paracrine signalling molecule.
In nervous system, immune system and circulatory
systems.
Diffuse...
NO
NO is also helps macrophages and neutrophils to kill
microorganisms.
CO, carbon monoxide is also used as a signal.
I...
Steroids
Small hydrophobic molecules.
Act as hormones.
Easily cross the membrane
Aldosterone – regulates blood pressur...
Neurotransmitters
Carry signals between neurons i.e., between
synapses.
Diverse group of hydrophilic molecules.
Hence t...
Action of neurotransmitters
Peptide hormones and growth factors
Widest range of signalling molecules in animals.
Size can range from few to a hundre...
Neuropeptides
 function as neurotransmitters as well as neurohormones.
 Examples: Enkephalins and endorphins
 They bot...
Polypeptide growth factors are signalling molecules
that control growth and differentiation of cells.
NGF (Nerve growth ...
Second Messengers
Second messengers are
 Substances apart from the signalling molecules
 Used to relay the message
 Us...
Identify the second messengers
Cell surface receptors
Stuctures on the plasma membrane
Each one has unique way of reacting to different
molecules to pe...
Forms of receptors
Steroid receptor
G protein coupled receptors
Tyrosine kinase receptors
Cytokine superfamily receptor
Steroid receptors
Found in cytosol, plasma membrane and the
nucleas.
Usually have nuclear receptors.
Lead to change in ...
Many G protien receptors and ion gated receptors
also act as steroid receptors.
Structure:
 Variable domain: the struct...
HDAC
Histone deacetylases (HDAC) are enzymes that
remove acetyl groups (O=C-CH3) from a histone.
allows the histones to ...
HAT
Histone acetyltransferases (HAT) are enzymes that
acytylate histone protiens by transferring a acetyl
group from acet...
Action of steroids
Tyrosine kinase receptors
It’s the largest group of enzyme linked receptors.
Have receptors for most polypeptide growth ...
Cytokine Receptors
called the cytokine receptor superfamily.
includes the receptors for most cytokines like
interleukin2...
G – Protein coupled receptors
Known as 7TM receptor or seven transmembrane
domain receptors.
They pass through the plasm...
Structure of G – protein linked receptors
Classification
Mechanism
The main response mechanism is by forming cAMP.
But there are 2 pathways:
 cAMP signalling pathway
 PIP pathway
cAMP pathway
PIP2 signal pathway
Desensitization
Three general ways
Inactivation
 They can become altered so they can no longer interact with G
proteins....
Rhodopsin like receptors
Rhodopsin is a seven pass transmembrane molecule.
Homologous to G protein coupled receptors.
A...
References
https://en.wikipedia.org/wiki/Cell_surface_receptor
https://www.boundless.com/biology/textbooks/boundle
http...
https://moodle.kent.ac.uk/external/mod/book/view
.php?id=2396&chapterid=79
http://bpsbioscience.com/cell-surface-recepto...
http://genome.tugraz.at/MolecularBiology/WS11_C
hapter_12.pdf
http://homepage.ntu.edu.tw/~mchuang/Receptor
%20signaling....
Cell adhesion and CAMs
 http://www.cryst.bbk.ac.uk/pps97/assignments/projects/emil
ia/Adh_mol.HTM
 https://www.rndsyste...
Cell surface receptors and signalling molecules
Cell surface receptors and signalling molecules
Cell surface receptors and signalling molecules
Cell surface receptors and signalling molecules
Cell surface receptors and signalling molecules
Cell surface receptors and signalling molecules
Cell surface receptors and signalling molecules
Cell surface receptors and signalling molecules
Cell surface receptors and signalling molecules
Cell surface receptors and signalling molecules
Cell surface receptors and signalling molecules
Cell surface receptors and signalling molecules
Cell surface receptors and signalling molecules
Cell surface receptors and signalling molecules
Cell surface receptors and signalling molecules
Cell surface receptors and signalling molecules
Cell surface receptors and signalling molecules
Cell surface receptors and signalling molecules
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Cell surface receptors and signalling molecules

Cell adhesion molecules, Introduction to cell signalling, signalling molecules and G protein coupled receptors

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Cell surface receptors and signalling molecules

  1. 1. BY C V ANURADHA I YEAR M.SC. HUMAN GENETICS Cell Surface Receptors, Signalling Molecules and G- protien couple receptors
  2. 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. 3. Introduction to cell signalling Cell signalling  Complex system of communication  Cellular activities  Cell functions are coordinated Main components involved:  Signalling molecules  Receptors
  4. 4. Cell surface receptors Specialized proteins In plasma membrane Integral proteins Help in communication
  5. 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. 6. What are the possible responses? Differentiation Proliferation Survival Cell specific responses
  7. 7. Modes of signalling Intracrine  Any hormone or ligand acting inside a cell  For example if they act through nuclear receptors.
  8. 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. 9. Juxtacrine signalling  Also known as contacct dependant signalling.  Proximity between cells is mandatory for signalling to take place.
  10. 10. Paracrine signalling  Cell to cell interaction  Signal is produced for adjacent cells  Ex: neurotransmitters in neurons
  11. 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
  12. 12. 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.
  13. 13. Cell – Cell interactions Three types based on the functions:  Tight junctions  Anchoring junctions  Communicating junctions
  14. 14. Tight Junctions Called occluding junctions. Connect the plasma membranes of adjacent cells. Prevent leakage of small molecules from between them.
  15. 15. 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.
  16. 16. Desmosomes connect the cytoskeletons of adjacent cells. hemidesmosomes anchor epithelial cells to a basement membrane. Proteins called cadherins form these links.
  17. 17. Communicating junctions Cells communicate with adjacent cells through direct connections, called communicating junctions. Direct physical contact is established. Allows small molecules to pass.
  18. 18. 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.
  19. 19. 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.
  20. 20. Classification of cell junctions
  21. 21. Based on localization between cells
  22. 22. 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.
  23. 23. Cell junctions based on functions
  24. 24. Adhesion by Cadherins and Integrins
  25. 25. Cadherin Integrin
  26. 26. Cadherins
  27. 27. Connexin Gap junction proteins Transmembrane proteins
  28. 28. 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
  29. 29. 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.
  30. 30. 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.
  31. 31. Types NO gas Steroids Neurotransmitters Peptide hormones and growth factors Second messengers
  32. 32. 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.
  33. 33. 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.
  34. 34. Steroids Small hydrophobic molecules. Act as hormones. Easily cross the membrane Aldosterone – regulates blood pressure Cortisol – Acts as a immunosuppressant
  35. 35. 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
  36. 36. Action of neurotransmitters
  37. 37. 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.
  38. 38. 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
  39. 39. 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.
  40. 40. 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
  41. 41. Identify the second messengers
  42. 42. Cell surface receptors Stuctures on the plasma membrane Each one has unique way of reacting to different molecules to perform functions.
  43. 43. Forms of receptors Steroid receptor G protein coupled receptors Tyrosine kinase receptors Cytokine superfamily receptor
  44. 44. 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.
  45. 45. 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.
  46. 46. 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).
  47. 47. 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.
  48. 48. Action of steroids
  49. 49. 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.
  50. 50. 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.
  51. 51. 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.
  52. 52. Structure of G – protein linked receptors
  53. 53. Classification
  54. 54. Mechanism
  55. 55. The main response mechanism is by forming cAMP. But there are 2 pathways:  cAMP signalling pathway  PIP pathway
  56. 56. cAMP pathway
  57. 57. PIP2 signal pathway
  58. 58. 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.
  59. 59. 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.
  60. 60. 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
  61. 61. 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
  62. 62. http://genome.tugraz.at/MolecularBiology/WS11_C hapter_12.pdf http://homepage.ntu.edu.tw/~mchuang/Receptor %20signaling.pdf http://www.columbia.edu/cu/biology/courses/w30 41/minden/cell_signaling_notes.pdf http://www.mhhe.com/biosci/genbio/raven6b/grap hics/raven06b/other/raven06b_07.pdf
  63. 63. 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

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