A3 cellular signalling pathways (spatial and temporal aspects) Flashcards
why do cells signal
coordination of day to day physiology
why do cells signal at a cellular level
cells respond and change to stimuli in their environmeny
cell communication failure and impairment leads to disorder, disease and death
what physiological activities rely on cell signaling
cell metabolism
cell growth
cell division
differentiation and development
coordination of gene expression
cell motility
cell morphology
cell death
what are the two types of cell signalling
intercellular signalling
intracellular signalling
explain intercellular signalling
communication between cells
-permits a single cell to influence the behaviour of other cells in a specific way
-synaptic transmission
explain intracellular signaling
signalling within the cell
-responding to extra and intracellular stimuli
what are intercellular signalling mechanisms
autocrine - cell targets itself
paracrine - a cell targets nearby cell
endocrine - cell targets distant cell through bloodstream
exocrine - acting on distant cell into a duct
juxtacrine - a cell targets a cell by gap junctions
examples of the 5 intercellular signalling mechanisms
autocrine- immune response T lymphocytes can stimulate own proliferation
paracrine - neutrophils
endocrine - progesterone and testosterone
exocrine - sweat glands
juxtacrine - delta and notch signalling
what intercellular signalling mechanisms does the liver use
endo and eco
insulin uses endo
bile uses exo
what is required for intracellular signaling cascades
second messengers
protein kinases (phosphorylation)
signal convergence/ cross talk to lead to key cell fates
what word is used to describe intracellular signaling cascades
network
its not linear, info and processes are received in many different complex ways
what environmental cues are cells bombarded by
chemical
mechanical
electrical
responses are intimately connected with what type of changes occurring within the 3D cell
spatially
what are the 4 major type of cell signal receptor with example
- ligand-gated ion channel receptors- nicotinic cholinergic
- g protein-coupled receptors- beta-adrenergic receptors binding epinephrine
- kinase linked receptors- insulin and growth factor
- nuclear receptors- estrogen
what does bias that exists with the extracellular signal, intracellular signal location impact
the kinetics of the response
what can influence cell signalling
diff cell-cell ECM interactions
formation of lipid microdomains
how can spatial and temporal dynamics be regulated
by physical barriers
eg cytoskeleton
where is canonical GPCR signalling initiated at
plasma membrane
can GPCRs be spatially (and temporally) compartmentalized
yes
what are signalosomes
large supramolucular complexes
composed of unique combinations of signalling pathway components
what are signalosomes targeted to and what do they allow cells
targeted to discreet intracellular localisation via the association of anchor or adptor proteins
allows cells to contruct the optimum cellular subdomain for sigalling
what are caveolae
specialized membrane microdomains
that form invaginations in the plasma membrane
what do caveolae function as
as platforms to recruit components of signal transduction pathways
and act as organising centres for signalling mols
sites of signal transduction
high levels of what coat caveolins
cholesterol, sphingolipids, and protein
GPCRs can generate unique signals from what
intracellular compartments
after internalisation of GPCR what do some receptors do
remain active
where are GPCRs internalised to
to endosomes and trafficked to pre golgi compartment
thyroid stimulating hormone receptor elicits different outcomes depending on the duration of receptor stimulation- what are the outcomes
30s stimulation = transient cAMP increase
>2 min = sustained cAMP increase
additional specificity in response
what is cAMP
a soluble second messenger and can freely diffuse in the cytosol
how can GPCRs have different effects when they produce the same second messengers
prostaglandin and adrenalin
what catalyses the breakdown of cAMP and how
phosphodiesterases (PDE)
by cleaving the P-O bond
role of PDEs
as well as catalysing the breakdown on cAMP
limiting diffusion of cAMP in cytosol
subcellular localisation of PDEs can regulate cAMP dynamics
what do measurable features of dynamic signals include
amplitude
frequency
duration
delay
cumulative level
why is taking measurements at appropriate timescale crucial
to capture true dynamical behaviour
timescale of the 4 intracellular receptors
- ligand gated ion channels
- milliseconds - GPCRs
- seconds - kinase linked receptors
-hours - nuclear receptors
-hours/days
what is compartmentalisation based on
expression of receptors and the intracellular memory
