Post on 15-Apr-2017
BYC V ANURADHA
I YEARM.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 molecules Types Functions
Cell surface receptors Introduction Structure Functions
G-Protien couple receptors
Introduction to cell signalling
Cell signallingComplex system of communicationCellular activitiesCell functions are coordinated
Main components involved:Signalling moleculesReceptors
Cell surface receptors
Specialized proteinsIn plasma membraneIntegral proteinsHelp in communication
Signalling molecules
Chemicals and other moleculesAct as ligandsBind to receptorVary in size, shape and structureSome are capable of carrying signal over
large distances
What are the possible responses?
DifferentiationProliferationSurvivalCell specific responses
Modes of signalling
Intracrine Any hormone or
ligand acting inside a cell
For example if they act through nuclear receptors.
Modes of signalling
Autocrine signalling Signal is to the same
cell. Signalling is by
binding with a cell surface receptor.
Not a nuclear receptor.
Juxtacrine signalling Also known as
contacct dependant signalling.
Proximity between cells is mandatory for signalling to take place.
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 stream Reaches target cell with
receptors
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.
Cell – Cell interactions
Three types based on the functions:Tight junctionsAnchoring junctionsCommunicating junctions
Tight Junctions
Called occluding junctions.
Connect the plasma membranes of adjacent cells.
Prevent leakage of small molecules from between them.
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.
Desmosomes connect the cytoskeletons of adjacent cells.
hemidesmosomes anchor epithelial cells to a basement membrane.
Proteins called cadherins form these links.
Communicating junctions
Cells communicate with adjacent cells through direct connections, called communicating junctions.
Direct physical contact is established.
Allows small molecules to pass.
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.
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.
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.
The basal lamina is a layer of extracellular matrix secreted by the epithelial cells.
Cytosolic plectin plate, integrin and lamins help in the formation.
Cell junctions based on functions
Adhesion by Cadherins and Integrins
Cadherin Integrin
Cadherins
Connexin
Gap junction proteinsTransmembrane
proteins
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
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.
Signalling Molecules
Messengers of cellsFor communicationThey can be compounds like peptides, amino
acids, steroids or even gases.Secreted by signalling cell.Carried out by exocytosis while some by
simple diffusion.
Types
NO gasSteroidsNeurotransmittersPeptide hormones and growth factors
Second messengers
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.
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.
Steroids
Small hydrophobic molecules.Act as hormones.Easily cross the membraneAldosterone – regulates blood pressureCortisol – Acts as a immunosuppressant
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
Action of neurotransmitters
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.
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 contractionVasopressin – stimulates water reabsorbtion
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.
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
Identify the second messengers
Cell surface receptors
Stuctures on the plasma membraneEach one has unique way of reacting to
different molecules to perform functions.
Forms of receptors
Steroid receptorG protein coupled receptorsTyrosine kinase receptorsCytokine superfamily receptor
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.
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.
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).
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.
Action of steroids
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.
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.
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.
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 waysInactivation
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.
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.
References
https://en.wikipedia.org/wiki/Cell_surface_receptor
https://www.boundless.com/biology/textbooks/boundless-biology-textbook/cell-communication-9/signaling-molecules-and-cellular-receptors-83/types-of-receptors-381-11607/
https://en.wikipedia.org/wiki/G_protein%E2%80%93coupled_receptor
http://www.ncbi.nlm.nih.gov/books/NBK9866/The Cell: A Molecular Approach. 2nd edition
by Cooper and Sunderland
https://moodle.kent.ac.uk/external/mod/book/view.php?id=2396&chapterid=79
http://bpsbioscience.com/cell-surface-receptorshttp://www.scq.ubc.ca/cell-surface-receptors-a-
biological-conduit-for-information-transfer/https://www.glowm.com/section_view/
heading/Cell%2520Membrane%2520Receptors/item/281 : Cell membrane receptors by C V Rao and Carolyn M Klinge
http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/moaction/surface.html
http://genome.tugraz.at/MolecularBiology/WS11_Chapter_12.pdf
http://homepage.ntu.edu.tw/~mchuang/Receptor%20signaling.pdf
http://www.columbia.edu/cu/biology/courses/w3041/minden/cell_signaling_notes.pdf
http://www.mhhe.com/biosci/genbio/raven6b/graphics/raven06b/other/raven06b_07.pdf
Cell adhesion and CAMs http://www.cryst.bbk.ac.uk/pps97/assignments/
projects/emilia/Adh_mol.HTM https://www.rndsystems.com/resources/articles/
adhesion-molecules-ii