Module 9: Cell Signalling

what is cell signalling

transferring information from the outside of the cell to obtain a response inside the cell

4 essential elements of cell signaling (both prokaryotic and eukaryotic)

signaling cell, signaling molecule, receptor molecule, responding cell

signaling in bacteria: how can bacteria take up DNA from the environment

small peptide binds to receptor on the surface of the cell —> bacterium expresses genes allowing it to take up environmental DNA

signaling in bacteria: low density of bacteria leads to __ peptide levels

low; [signal peptide] is too low therefore gene expression is turned off

signaling in bacteria: high density of bacteria leads to __ peptide levels

high; peptides bind to the receptors and stimulate DNA uptake

adrenaline

signaling molecule released by the adrenal glands, can bind to receptors in the heart (or other organs) to stimulate a response

4 steps of signaling between cells

receptor activation, signal transduction, cellular response, signal termination

ligand

signaling molecule; binds to the receptors and can be extracellular (secreted by cells) or intracellular

cell signaling: receptor activation

ligand binds to ligand binding site on receptor and conformational change occurs. this triggers chemical reactions in the cytosol

cell signaling: signal transduction

receptor transmits a message, can remain in cytoplasm or go to nucleus by activating/inactivating a series of proteins

cell signaling: response

response could activate enzymes, genes, signal other cells or cause cell to divide/change shape depending on the cell type

what happens when epinephrine binds to the heart muscles vs smooth muscle

causes heart to contract strong and fast (can be GPCR system) but relaxes smooth muscle in the airways

what happens when a cell has received and responded to a signal

signal is terminated to stop the cellular response

in multicellular organisms, communication happens between cells within (same/different) organism. how can the distance be discribes

same but distance between cells varies

2 classifications of cell communication

long distance and short distance

endocrine signaling

long distance communication, signaling molecules travel the bloodstream

what are the chemical signaling molecules in endocrine signaling and what produces them

hormones, produced by endocrine cells

paracrine signaling

short distance (~20 cells) communication between neighboring cells

autocrine signaling

cell secreted signal that acts on itself

what are paracrine and autocrine signaling important for

multicellular organisms’ embryonic development

contact-dependent signaling

signaling occurring from direct contact in neighboring cells

alternate name for contact-dependent signaling

juxtracrine signaling

what kind of signaling molecules pass easily through membrane

non polar therefore don’t need a receptor on the outside

how do nonpolar ligands trigger cell signaling

go inside the cell and activate receptor proteins in the cytosol or nucleus

what receptors must polar ligands bind to

transmembrane, cell surface receptors

how are extracellular receptors activated

ligand binding triggers conformation change, this activates the receptor

what are the 3 classifications of cell surface receptors

g protein-coupled receptors (GPCRs), receptors kinases, ion channels

importance of GPCRs

found in almost every eukaryote

what do GCPRs associate with

g-proteins (contain GTP/GDP)

what are the 3 subunits of the G proteins

alpha, beta, gamma

what g protein subunit binds to GTP/GDP

alpha subunit

when are all 3 subunits of the G protein bound together

when the alpha subunit is bound to GDP

when is the G protein active

when the alpha subunit is bound to GTP

when is the G protein inactive

when the alpha subunit is bound to GDP

what is the purpose of GTP/GDP binding to the protein subunit

regulation

what happens when a ligand binds to GPCR

activates G protein by switching GDP with GTP, allowing alpha subunit to dissociate from and bind to target protein for activation

example of GPCR

heart rate, controlled by epinephrine from the adrenal gland

common name of epinephrine

adrenaline

GPCR system of adrenaline

epinephrine binds to the GPCR, alpha subunit binds to adenylyl cyclase.

• activated adenylyl cyclase coverts ATP to cAMP → activates protein kinase A (PKA) → phosphorylates heart muscle protein → faster heart rate

cAMP

cyclic AMP which is a small signaling molecule

in the example of epinephrine GPCR signaling, cAMP is a ___ messenger

secondary

how long does GPCR of adrenaline in the heart keep the heart rate up for

as long as epinephrine is bound to the receptor

signal amplification

small amount of ligand producing a large response in the target cell, happens with GPCR signalling

which 3 places in the ephinephrine GPCR system amplified

• each epi-bound receptor activates multiple g proteins

• each adenylyl cyclase produces lots of cAMP

• each active PKA activates multiple protein targets

what is binding affinity in cell signaling

how tightly receptor holds a ligand; controls how long a ligand stays bound

what are the 5 levels of signal termination for epinephrine GPCR system

• epinephrine leaves receptor

• g protein coverts GTP to GDP (deactivates)

• adenylyl cyclase deactivated, no more cAMP

• cytosol enzymes degrade cAMP

• phosphatases remove phosphate groups from activated proteins

what do kinases do

remove phosphate group from ATP and add to protein to activate it

what do phosphatases do

remove a phosphate group from an active protein to deactivate it; t for take away

when are receptor kinases activated

when ligand binds, causes dimerization

what is receptor kinase dimerization

when receptor associates in a dimer (2 halves form the whole)

process of cell signaling with receptor kinases

ligand binds to the receptor kinase → dimerization → phosphorylation → phosphates provide binding site for intracellular signaling proteins

examples of receptor kinases systems

formation/elongation of limb buds that form arms and legs, insulin signaling for glucose transport into the cell, wound healing

PDGF

platelet derived growth factor

kinase receptor pathway for papercut

blood encounters cut → platelets release PDGF → PDGF binds to PDGF receptor kinase →dimerization →phosphorylation → phosphorylated receptor helps activate other proteins

MAP kinase pathway: what cytoplasmic signaling protein is activated and what happens

GTP bound (activated) Ras; triggers 3 kinase cascade and at the end, activated kinase enters nucleus to activate cell division genes

when is the MAP kinase pathways terminated

when GTP is replaced with GDP in Ras

ion channels can…

change ion flow across the cell and can be gated

what are the 3 types of gated ion channels

ligand gated, voltage gated, and mechanically gated

ligand gated ion channel

respond to binding of signalling molecule

voltage gated ion channel

respond to voltage change in the cell

mechanically gated ion channel

response to force applied to cell

what is the purpose of gated ion channels

regulates ion movement

when the ion gate is closed

prevents the movement of the ion

when the ion gate is open

allows movement of the ion