Transcript The same signaling molecule can induce - Lectures For UG-5

Cell Signaling (Lecture 2)
Types of receptors
Classification of hormones
Lipophillic Hormones with intracellular
receptors e.g steroid, thyroxine, retinoic
acid
 Hydrophillic with cell-surface receptors
e.g peptide hormones (insulin growth
factor and glucagon), small charge
molecules (epinephrine and histamine)
 Lipophillic with cell surface receptor e.g.
prostaglandins
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Each Cell Is Programmed to Respond to Specific
Combinations of Signaling Molecules
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Each cell is exposed to many different signals known as
combinatorial signaling.
Each cell type displays a set of receptors that enables it to
respond to a corresponding set of signaling molecules.
These signaling molecules work in combinations to regulate the
behavior of the cell. Many cells require multiple signals ( green
arrows) to survive and additional signals ( red arrows) to
proliferate; if deprived of all signals, these cells undergo
programmed cell death.
The same signaling molecule can
induce different responses in different
target cells
Cell Surface Receptors
General elements of GPCRs
Most abundant class of receptors
 Found in organisms from yeast to man
1. A receptor with 7 membrane-spanning
domains
2. A coupled trimeric G protein
3. A membrane bound effector protein
4. Feedback regulation and desensitization of
the signalling pathway
5. A 2nd messenger present in many GPCRs.
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Second messengers are molecules that
relay signals from receptors on the cell
surface to target molecules inside the cell, in
the cytoplasm or nucleus.
 These components of GPCRs can be mixed
and matched to achieve an astonishing
number of different pathways
 GPCR pathways usually have short term
effects in the cells
 Allow the cells to respond rapidly to a
variety of signals like environmental stimuli
(light) or hormonal stimuli (epinephrine)
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General features
 GPCRs have same orientation in the
membrane , 7 transmembrane alphahelical regions, 4 extra cellular segments,
4 cytosolic segments
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The exterior surface of all GPCR
consists of hydrophobic amino acids
 Amino acids allow the protein to be
stably anchored in the hydrophobic core
of the plasma membrane
 The amino acids are diverse
 Which allow different GPCR to bind very
different small molecules
 These small molecules can be hydrophilic
(epinephrine) and hydrophobic (retinol or
odorant)
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G Protein
•Guanine nucleotide-binding
proteins, family of proteins involved in
transmitting chemical signals originating
from outside a cell into the inside of the
cell.
•G proteins function as molecular
switches. Their activity is regulated by
their ability to bind to and
hydrolyze guanosine triphosphate (GTP)
to guanosine diphosphate (GDP).
•When they bind GTP, they are 'on', and,
when they bind GDP, they are 'off'.
•G proteins belong to the larger group
of enzymes called GTPases.
Gβ§
Various ligands use G-protein-coupled receptors (GPCRs) to stimulate membrane,
cytoplasmic and nuclear targets. GPCRs interact with heterotrimeric G proteins
composed of , and subunits that are GDP bound in the resting state. Agonist binding
triggers a conformational change in the receptor, which catalyses the dissociation of
GDP from the subunit followed by GTP-binding to G and the dissociation of G from
G subunits1. The subunits of G proteins are divided into four subfamilies: Gs, Gi, Gq and
G12, and a single GPCR can couple to either one or more families of G proteins. Each G
protein activates several downstream effectors.
Activation cycle of a G-protein by a G-proteincoupled receptor receiving a ligand
Different G proteins are activated by
different GPCRs and inturn regulate
different effector proteins.
 Effector proteins are in GPCR pathways
are either membrane bound ion channels
or enzymes that catalyze the formation of
the second messengers.
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GPCR that regulate ion channels
The simplest cellular responses to a signal is the
opening or closing of ion channels essential for
transmission of nerve impulses
 Nerve impulses are essential to the sensory
perception of environmental stimuli (light, odor) to
transmission of information to and from the brain
and to the stimulation of muscle movement
 During transmission of nerve impulses, the rapid
opening and closing of ion channels causes changes
in the membrane potential
 Some neurotransmitter receptors are GPCRs whose
effector proteins are Na or K channels
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Neurotramsmitter binding to these receptors
causes the associated ion channel to open or
close leading to changes in the membrane
potential e.g acetyl choline involved in K
transport