LIFESCI 7C Lecture Notes - Lecture 1: Autocrine Signalling, Paracrine Signalling, Transmembrane Protein
Week 1
9.1 Principles of Cell Communication
● Cells receive info from physical environment, other cells and respond to signals by changing activity or dividing
● Basic principles of cell communication (receiving and responding to signals first evolved from unicelluar
organisims and apply to all cells
Cells communicate using chemical signals that bind to specific receptors
● Four elements of cell signalling
○ signaling cell The source of the signaling molecule.
○ signaling molecule The carrier of information transmitted when the signaling molecule binds to a
receptor; also referred to as a ligand.
■ Vary immensely: peptides, lipids, gases, etc; carry info from one cell to the next
○ receptor protein The molecule on the responding cell that binds to the signaling molecule.
■ presence/absence of receptors allow signalling to be specific for particular cells
○ responding cell The cell that receives information from the signaling molecule.
● Ex: bacterial density and rate of DNA uptake (increased w/ greater density) → fueled by signalling to indicate
presence of other bacteria
○ → quorum sensing: process by which bacteria are able to determine high/low population density and turn
on specific genes across the entire community; used to control/coordinate many different types of
bacterial behaviors
Signalling involves receptor activation, signal transduction, response, and termination
● When signalling molecule binds to receptor on responding cell….
1. receptor activation The “turning on” of a receptor, which often occurs when a signaling molecule binds
to a receptor on a responding cell.
a. Receptors can be activators, enzymes, channels, etc
2. signal transduction The process in which an extracellular molecule acts as a signal to activate a
receptor, which transmits information through the cytoplasm → chain rxn of molecule activation
a. Signal often amplified at each step in the pathway→ low signal concentration can have large
effect on responding cell
3. response A change in cellular behavior, such as activation of enzymes or genes, following a signal.
4. termination the stopping of a signal; response can be terminated at any point in signalling pathway
a. Protects cell from overreacting to existing signal→ appropriate level of response
b. Allows cell to respond to new signals
● In general elements of signal transduction have been evolutionary conserved over long periods of time in a wide
range of organisms
9.2 Cell Signaling over Long and Short Distances
● In multicellular organisms, distance between communicating cells varies considerably
○ Far cells: signaling molecule transported by circulatory system (endocrine signaling)
○ Close cells: signaling molecule moves by diffusion (paracrine signaling)
○ Physicall attached cells: signaling molecule is not released from the signaling cell at all (contact-
dependent signaling)
○ Self-signaling: autocrine signaling
Endocrine Signaling acts over long distances
● endocrine signaling Signaling by molecules that travel through the bloodstream.
○ E.g. adrenaline, estradiol (estrogen) and testosterone (androgen)
Signaling can occur over short distances
● paracrine signaling Signaling by a molecule that travels a short distance to the nearest neighboring cell to bind
its receptor and deliver its message; moves by diffusion!
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○ growth factor Any one of a group of small, soluble molecules, usually the signal in paracrine signaling,
that affect cell growth, cell division, and changes in gene expression (type of signaling molecule).
■ Type of signalling molecule that tells responding cell to grow, divide, or differentiate
■ Secreted by embryonic cells to influence neighboring cells→ help shape structure of adults’ tisues,
organs, limbs
○ Ex: Neuron-neuron or neuron-muscle short-range signaling
● autocrine signaling Signaling between different parts of a cell; the signaling cell and the responding cell are one
and the same.
○ Ex: specialized cell can use autocrine signaling to maintain this developmental decision; can also be used
by cancer cells to promote cell division
Signaling can occur by direct cell-cell contact
● Transmembrane proteins on surfaces of signalling and and responding cell act as signalling molecule and
receptor→ signaling molecule not released but remains associated w/ plasma membrane of signaling cell
○ Important in embryonic development
● E.g. glial cells (responding cell), Notches (receptors), neurons (signaling cell) and Delta proteins (signaling
molecule)
● Signal molecules that are polar usually have their corresponding receptor on the surface of the cell
○ Nonpolar signal molecules can pass through plasma membrane of responding cell and bind to receptors
inside the cell
9.3: Cell-Surface and Intracellular Receptors
● Receptors: proteins that receive/interpret info carried by signaling molecules
○ Signal molecule=ligand
○ ligand-binding site The specific location on the receptor protein where a signaling molecule binds; bond
is noncovalent and highly specific!
○ Ligand binding to receptor’s ligand-binding cite causes conformational change in receptor
■ Conformational change activates the receptor→ receptor passes message from signaling
molecule to cell interior; triggers chem reactions/other changes in cytosol
Receptors for polar signaling molecules are on the cell surface
● Location of particular receptor depends on polarity of signaling molecule
○ Polar signaling molecule (cannot cross through plasma membrane)→ cell-surface receptors
○ Nonpolar signaling molecule (can cross through plasma membrane) → intracellular receptors
● Receptor proteins for growth factors/other polar ligands=transmembrane proteins w/ extracellular, transmembrane
and cytoplasmic parts
○ ENTIRE receptor protein undergoes conformational change upon binding w/ ligand→ receptor=bridge
between inside/outside of responding cell, carrying hydrophilic signal’s message across hydrophobic core
of plasma membrane
Receptors for nonpolar signaling molecules are in the interior of the cell
● Nonpolar signaling molecules like steroid hormones (endocrine) are hydrophobic and pass through plasma
membrane and into cell easily
○ Once inside steroid hormones bind to receptor proteins in cytosol or nucleus to form receptor-steroid
complexes whcih enter nucleus and act to control expression of genes
○ Steroid receptors ON nucleus often already bound to DNA and only need steroid to turn on gene
expression
● Ex: sex hormones, glucocorticoids, ecdysone, etc
Cell-surface receptors act like molecular switches
● Many receptors act as binary molecular switches: “on” when bound to signaling molecule or “off”
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● G protein-coupled receptor A receptor that couples to G proteins, which bind to the guanine nucleotides GTP
and GDP.
○ are evolutionary conserved and all have a similar molecular structure
● receptor kinase A receptor that is an enzyme that adds a phosphate group to another molecule.
○ catalyzes the transfer of a phosphate group from ATP to a substrate
○ Phosphorylation by a kinase switches a protein on
■ Added phoshpate group can alter protein shape or provide new protein binding sites
○ phosphatase An enzyme that removes a phosphate group from another molecule.
■ Dephosphorylation switches a protein off
● ion channels Cell-surface receptors that open and close, thereby altering the flow of ions across the plasma
membrane.
○ Ion channels open/close in different ways
■ Open in response to changes in membrane voltage
■ Open when bound to ligand (ligand-gated ion channels)
○ Helps ions/molecules diffuse in/out cell by providing hydrophilic pathway
○ Channels usually closed, but opens when signaling molecule binds to extracellular portion of lignad-gated
ion channel → conformational change → opens
9.4: G Protein-Coupled Receptors and Short-Term Responses
● G protein-coupled receptors=large family of cell-surface molecules found in virtually every eukaryotic organism;
shared characteristics result from shared evoluiotnary history
○ Have similar structure: single polypeptide chain that have 7 transmembrane spanning regions w/ ligand-
binding site outside the cell and G protein binding portion inside the cell
○ When activated, associate w/ G protein
● Able to respond to diverse set of signaling molecules: hormones neuotransmitters, small molecules, etc. w/
diverse effects
○ Evolved from sensory receptors in unicellular eukaryotes
The first step in cell signaling is receptor activation
● Activated G protein-coupled receptor binds to (couples w/) G- protein--causes G protein to release GDP and bind
GTP (activating it) → G protein goes on to activate additional proteins in signaling pathway
● G-protein has two states: on and off; able to bind to guanine nucleotides GTP and GDP
○ Bound to GTP=on; bound to GDP=off
● G-protein consists of γ subunits, α (alphGDP a), (beta), and (gamma) subunits
○ α subunit binds to either or GTP, when GTP replaces GDP, α subunit separates from other two
■ In most cases, it is the isolated GTP-bound α subunit that is now active and able to bind to target
proteins in the cell
Signals are often amplified in the cytosol
● Adrenaline binds to g protein-couple receptor→ g-protein activated → GTP bound subunit binds to and activates
enzyme adenylyl cyclase → enzyme converts ATP to cAMP → cAMP binds to/activates another molecule, protein
kinases A (PKA)
○ Cyclic AMP= second messenger An intermediate cytosolic signaling molecule that transmits signals
from a receptor to a target within the cell. (First messengers transmit signals from outside the cell to a
receptor.)
● Signal amplification of adrenaline: small amount of signaling molecule has large effect on responding cell
○ Single receptor bound to adrenaline can activate SEVERAL G proteins
○ Each molecule of adenylyl cyclase catalyzes production of large amounts of cAMP
○ Each PKA molecule activates multiple protein targets by phosphorylation
Signals lead to cellular response
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Document Summary
Cells receive info from physical environment, other cells and respond to signals by changing activity or dividing. Basic principles of cell communication (receiving and responding to signals first evolved from unicelluar organisims and apply to all cells. Cells communicate using chemical signals that bind to specific receptors. Signaling cell the source of the signaling molecule. Signaling molecule the carrier of information transmitted when the signaling molecule binds to a receptor; also referred to as a ligand. Vary immensely: peptides, lipids, gases, etc; carry info from one cell to the next receptor protein the molecule on the responding cell that binds to the signaling molecule. Presence/absence of receptors allow signalling to be specific for particular cells responding cell the cell that receives information from the signaling molecule. Ex: bacterial density and rate of dna uptake (increased w/ greater density) fueled by signalling to indicate presence of other bacteria.
