The document provides a comprehensive overview of cell surface receptors, signaling molecules, and G-protein coupled receptors, highlighting their roles in cell signaling and communication. It explains various modes of signaling, types of cell junctions, and adhesion mechanisms that facilitate cell interactions and communication. Additionally, it discusses the classification and functions of different signaling molecules, receptors, and second messengers involved in cellular processes.

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

28. Cadherin Integrin

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

44. Action of neurotransmitters

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.

57. Action of steroids

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

70. PIP2 signal 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

79. 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

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