cell signalling Flashcards
why do cells communicate
- Respond to immediate environment – including danger signals
- Respond to central commands
- Respond to local commands
- Respond accordingly
- Coordinate cellular responses
- Integrate signals from multiple sources
- Induce / decrease growth (division) if the need arises
what are the 3 types of intercellular signalling
chemical
physical
gaseous
what is intercellular signalling
between cells
what are signalling molecules that bind and activate receptors
agnosits/ligands
what are signaling molecules that bind to and inactivate receptors
antagonists/blockers
what are transmembrane/ cell surface receptors
Respond to signals on the outside of the cell by interacting with molecules on the inside
what are the types of transmembrane / cell surface receptors
G protien coupled receptors (GPCRs)
ion channel linked receptors
enzyme receptors
why are transmembrane receptors important
- Most signalling molecules are too large or too hydrophilic to cross the membrane
- Ligand binding changes the activities of the intracellular domains of the receptor, which initiates the response
- The signalling molecule itself doesn’t need to enter the cell
what kind of receptor is this
cytoplasmic and nucelar
what are cytoplasmic and nuclear receptors
- Small molecules and hydrophobic molecules can cross the cell membrane
- Bind directly to receptors in the cytosol or the nucleus
what kind of receptor is this
transmembrane
what determines how different cells can respond differently to the same signal
The sets of receptors the cell has
The intracellular machinery
This explains why drugs sometimes have additional unwanted effects
what are the 5 modes of intercellular signalling
endocrine
paracrine
neuronal
autocrine
juxtacrine
which types of intercellular signalling is long range
endorcine
which types of intercellular signalling are short range
paracrine
neuronal
autocrine
juxtacrine
what is a hormone
a compound produced by an endocrine gland and released into the bloodstream where it acts on target cells at a distance location
what is endocrine signalling
- low chemical communication
- Hormones are released and circulate in the blood, coming into contact with most cells within the body (hence long distance)
why can only a limited number of cells respond to a hormone?
must express the correct receptor to interpret the signal
what do hormones do during intercellular signalling
Hormones regulate cell reactions by affecting gene expression
what is paracrine signalling
- Signalling molecules are released from one cell and diffuse locally to neighbouring cells
what are kinds of paracrine signals
proteins
amino acid derivatives
dissolved gas
what kind of signalling is this?
paracrine
what is neuronal/ neurocrine signalling
- Deriving from a nerve
- Neurotransmitters travel only across the synaptic gap to the adjacent target cell only (e.g. nerve cell, muscle cell)
what is an example of neuronal signalling
noradrenaline, secreted form sympathetic nerve terminal to act at adrenoceptors to contract blood vessels
what kind of signaling is this?
neuronal
what is autocrine signalling
Cells secrete signalling molecules that bind their own receptors to generate a change in their own behaviour
what is an example of autocrine signaling
- Example: cytokine interleukin-1 in monocytes
- Interleukin-1 is produced in response to external stimuli
- Binds to cell-surface receptors on the same cell that produced it
how does autocrine signalling maintain homeostasis
Sometimes the binding to their own receptors can lead to an increase (positive feedback) or decrease (negative feedback) the molecule production
what is juxtacrine signalling
- Contact-dependent signalling: immediate neighbours signal to eachother via membrane bound molecules
- Does not require the release of a signalling molecule
what are examples of juxtacrine signalling
contact dependant ligang binding
communication junctions- gap junctions
what is contact-dependant receptor-ligand binding
type of juxtacrine signalling
direct cell to cell communication or interactions with the extracellular matrix (ECM)
what is an example of contact-dependant receptor-ligand binding
Antigen presentation requires contact between the two cell types
what are communication junctions
tpye of juxtacrine signaling
Provide neighbouring cells with a direct communication link that can be opened or closed in response to the cell environment similar to an ion channel
what are the features of communication junctions?
- Channels form between cells allowing diffusion of small molecules such as ions, nucleotides and sugars
- Narrow pore spanned by pore-forming proteins called connexins
- Provide rapid metabolic and electrical coupling
what is an example of a gap junction
- Gap junctions between heart muscle cells allow waves of electrical excitation to pass quickly through the tissue
- Gap junctions appear in the myometrium of the uterus towards to the end of pregnancy, where they help coordinate uterine contractions during childbirth
what are 2 examples of endocrine signalling
insulin
stress response
what is the insulin endocrine signalling response
secreted from pancreas
released into the bloodstream
act at insulin receptors to promote glucose
what are the signalling errors of insulin
Type 1 diabetes- no insulin made
type 2 diabetes- absent or decreased response to insulin by target cells
what is the endocrine signalling response for stress response
cortisol binds to the glucocorticoid receptor (GR)- can both activate and suppress gene expression
produce both metabolic and anti-inflammatory effects
what are the clinical uses of corticosteroids
synthetic compounds that activate GR
autoimmunity, allergic reactions, asthma
what are examples of paracrine signalling
nitric oxide
what is the features of nitric oxide in paracrine signalling
produced by nitric oxide synthase (NOS) and diffuses into nearby smooth muscle cells and activates its target enzyme
short half-life
what does NO cause
causes vasorelaxation, platelet aggregation and immune responses
reduced levels in most cardiovascular disorders
what does receptor activation lead to
intracellular signalling cascades and second messenger systems
how are signals created by messengers turned off
Chemical signals are enzymatically degraded
G proteins become inactivated by GTPases
what are the 3 stages of intracell communication
reception
transduction
response
what is reception in intracell communication
a chemical message binds to a protein on the cell surface
what is transduction in intraacell communication
the binding of the single molecule alters the receptor
this starts a cascade of reactions
what is response in intracell communication
the transduction pathway triggers a response
this can be: turning on a gene, activating an enzyme, rearranging the cytoskeleton
how are signalling molecules controlled
By post translational modification, e.g. phosphorylation
By regulating whether a G protein has bound GDP or GTP
By provision of activators such as Ca2+ and cAMP
what is a kinase
Kinase is an enzyme that phosphorylates proteins
what do kinases do
add a phosphate group
what is phosphatase
enzyme that dephosphorylates proteins
what are examples of serine/threonine kinases
CAMK- ca+
PKA
PKC
MAPK
what are 2 types of tyrosine kinases
non reeptor and receptor tyrosine kinases
what are integral membrane proteins
Integral membrane proteins transmit the signal into the cell; these receptors span the membrane.
what molecules cant cross the lipid bilayer
proteins
peptides
charged molecules
how do ligands interact with receptors
Ligands may interact directly with the receptors or by binding to co-receptors or accessory molecules on the cell surface
what happens when transmembrane receptors are activated
Receptor activation causes a conformational change in the tertiary or quaternary structure that allows initiation of signalling
how are ion channels structured
5 transmembrane subunits come together to form a channel
what do ion channels transport
K+
Na+
Ca+
Cl-
what are the 2 responses ion channels open to
Changes in the transmembrane potential: Voltage-gated ion channels
A chemical binds: Ligand-gated ion channels / ionotropic receptors
what are features of ion channels
FAST regulated opening/closing mechanism
Once activated, allow ions to move through - changes the electrical properties of the cell
what are Ligand-gated ion channels / Ionotropic receptors
Transmembrane proteins consisting of a receptor part and a channel which traverses the membrane
Open in response to binding of a ligand
Once activated will still allow ions to go through (Na+, K+, Ca2+, Cl-) however they are classified according with the ligand binding to them
what are examples of ligand gated ion channels
nicotinic- acetylcholine receptor
GABA receptor
Glycine receptor
5-HT3 receptor
what are features of G-Protein coupled receptors (GPCRs)
Largest group of receptors
A single long polypeptide chain folded 7 times into a globular shape with portions inside and outside of the cell
Interact with G proteins in the plasma membrane that have 3 subunits; α, b and y
what are the 3 types of Ga proteins
Gai/o
Gas
Gaq
why are there 3 different types of Ga proteins
coupled to different intracellular signalling pathways
what are second messenger systems
Second messenger systems - concentration changes in response to receptor activation by agonist
what is the Gai protein signalling pathway
GPCR
Gai protein
adenylyl cyclase
cAMP
PKA
what is the Gaq protein signalling pathway
GPCR
Gaq protein
phospholaise c (PLC)
Diacylglycerol (DAG) -> protein kinase C (PKC)
IP3 -> Ca2+ released from the ER -> PKC
what is the by subunit signalling pathway
GPCR
by subunit
K+ channel
K+ move out the cell
what are features of enzyme linked receptors
These receptors usually have a single membrane spanning domain
The cytoplasmic enzymes that induce signalling are normally protein tyrosine kinases
Extracellular ligand binding domain, a single transmembrane helix, a cytoplasmic region containing the protein tyrosine kinase activity
what are features of receptor tyrosine kinases
Ligand binding activates enzyme activity within the cytoplasmic domain
The response usually requires receptor dimerisation
Tyrosine residues in the intracellular domains are auto-phosphorylated in response to the signal
Typically, responses are slow
what are features of cytoplasmic/nuclear signalling
For signals that can cross the cell membrane
Alter gene transcription (and hence protein levels) directly
