Module 4 Flashcards
Extracellular communication
signal is received from the outside of the cell
intracellular communication
( cell will collect info, synthesize the info and make decision) external communication will cause internal changes
direct cell to cell communication can be described as
Gap junctions
what are gap junctions?
made up of connexons that dock together to form channels from one cell to another, chemicals can move directly between cells
what can pass through gap junctions ?
small particles such as ions and signalling molecules - they are highly regulated and can open the door when needed ( thought to be a self defence mechanism )
how do cells communicate with each other when they arent touching ?
they will communicate through secretions where there are 4 types of secretions that can be distinguished by the type of cell or the location of the cell recieving the signal
autocrine secretions
released by a cell and have the same effects on a cell
paracrine secretions
released by cell and have effect on nearby cells
endocrine secretions
released by cell and will have effect on distant cell
neurotransmitters
released by the nerve terminal into the synapse
what is a lysosome?
organelles that break down misfolded and damaged organelles, nucleic acids, lipids etc
what is proteosomes ?
protein complexes that break down dmaged and misfolded proteins in the nucleus and cytosol
what are peroxisomes
take care of dangerous free radicals including ROCS, ALSO involved in the decomposing long chains of fatty acids, and cargo like uric acid
How will cargo get to the lysosome ?
-misfolded proteins and cellular content will tagged for the lysosome
-cargo is delivered to the lysosome via the endomembrane system
-M6P sugar tag on the cargo will send it to the lysosome along with proteases( same sugar tag)
-Vesicles will fuse with the lysosome where its contents will be emptied and digested by the proteases
What do lysosomes contain ?
high concentrations of proteases which are capable of cleaving membrane proteins and proteins in the lysosome
- also contain enzymes that are able to digest sugars and fats and can engulf damaged organelles –> will break down large molecules into basic parts that will be recylced back to the cytosol to be reused
what happens to the cytosolic proteins in the proteasome ?
will be tagged with a polyubiquitin chain which has multiple molecules of ubiquitin which is needed for the proteosome to recognize and degrade the proteins
explain nuclear proteins with proteasomes?
proteasomes can also be found in the nucleus which allows them to degrade nuclear proteins ( not export to cytosol )
describe peroxisomes
small organelles which contain enzymes that catalyze reactions . Specifically they are the place where Reactive oxygen species can be dealt with safely
what are the proteins in the peroxisomes called ?
peroxins which are synthesized in the cytosol and use targeting signals( PTS) to make there way to the peroxisome
what is apoptosis ?
known as programmed cell death, where it is used as form of protection for the body against cells that no longer function properly
what are the 4 steps in apoptosis ?
- initiation
- membrane blebbing and enzyme activation
- cell structure changes
- engulfment
how is apoptosis initiated ?
can be started from both intrinsic and extrinsic pathways,
intrinsic pathway of apoptosis ?
starts from outer membrane of mitochondria, and the pathway will get activated when there is severe DNA damage or ROS or toxins or trauma
extrinsic pathway in apoptosis ?
starts from external signals , begins at the plasma membrane receptor known as the death receptor in which neighbouring cells will release death ligands that will bind to receptor and start process
what is membrane blebbing ? and which enzymes are activated ?
when the cell begins to form protrusions or shrinks and is the first sign of apoptosis . Caspases enzymes are activated by both pathways and will cleave and activate more caspases called executioner capsases
what are the structural changes seen in the cell ?
executioner caspases will cause DNA to become fragmented and nuclear membrane will break down , the cytoskeleton will disassemble and the phospholipid content in the plasma membrane changes , organelles will persist and will be enclosed in apoptotic bodies
what happens in engulfment ?
phagocytes will endocytose the apoptotic bodies to dispose of them which are then safely digested by lysosomes of the phagocytes creating minimal disturbance in the cell
what is necrosis and when does it happen?
takes place from cellular injury in which the cell will try and repair itself - it is the pathway of cell death when a cell is beyond repair and the organelles dont function so the cell dies
what are the 3 steps in necrosis ?
Damage , swelling and destruction
how is damaged caused
toxins, extreme heat or radiation, freezing, ischemia , pathogens mechanical trauma
what happens in swelling ?
the organelles will lose there structure and start to swell where vacuoles will form and DNA may also be degraded depending on the damage
what happens in destruction ?
structural integrity will be lost and the contents of the cell spill out because of small holes causing inflammatory signals
Proteins of the mitochondria will be released and exposure of lysosomal contents where nearby cells will also get damaged
what are the steps in the protein kinase signalling cascade
1) Fibroblast growth factors (FGFs) can stimulate cell growth and will bind to FGF receptors ( FGFR)
2)binding will cause subunits to dimerize ,FGFR will undergo tryosine transautophosphorylation , to create phosphotyrosines on the cytoplasmic side which will be able to bind to different proteins
3)phosphotryosine can bind to Grb2 an adapter protein which will create a conformational change and allow it to bind to SoS, causing its activation an allow SoS to bind to Ras
4) Binding of SoS to Ras will replace GDP with GTP causing Ras to activate allowing it to bind to serine kinase known as Raf
5) Activated Raf will phosphorylate protein kinase MEK which will phospohorylate serine/ threonine kinase ERK allowing it to phospohorylate proteins in the cytosol and neucleus
what are the steps in phospholipid kinase signalling cascade
1) Ligand binds to GPCR letting the receptor to interact with heterotrimeric G protein - this will stimulate the replacement of GDP for GTP in G alpha subunit allowing the heterotrimeric protein G protein disassociate from the receptor from receptor and leave Beta Y subunit and activated Ga- GTP
2)Ga- GTP will bind to the phospholipid kinase signalling protein (phospholipidase C , PLC) which will break down PIP2 to release second messengers, DAG and IP3
3) IP3 will diffuse freely in cytosol and activate its receptor and activate its receptor on the ER opening ligand gated CA+ channel where Ca+ will act as a second messenger actviating calcium binding proteins
What is another name for signals ?
Ligands, which come from extracellular space and needs to bind to a receptor known as a signal tiggering molecule which will bind to site on target protein
what are the 3 kinds of ligands ?
membrane impermeable. membrane permeable and physical receptors
membrane impermerable ligands
most signals, which must bind to receptors on cell surface because they cannot penetrate membrane
membrane permeable ligands
mainly steroids, can penetrate the membrane and are not limited to membrane receptors as they can bind with cytosolic receptors as well
physical signals
include pressure temperature and light
what are the 6 classes of receptors ?
G protein coupled receptors, guanylate cyclase , protein kinase receptors , transmembrane scaffolds , nuclear receptors ion channels
GPCR structure
contains 7 transmembrane domains (h1-h7) and a Heteromeric G protein that with Alpha ,Beta and Gamma subunits
GPCR function
binding of GPCR to receptor will cause a conformational shape change in the receptor leading to the activation of the G protein subunits
Ion channel receptors functions
AKA, ligand gated channels , transmit signal information by permitting ions to flow through from one side to the other –> when specific ligand binds the channel will go through conformational change that opens the pores , do not use enzymes
ion channels are responsible for
voluntary muscle contraction and is used for nerve cell communication
guanylate cyclase
found as being bound to the membrane and in soluable form in cytosol
structure of guanylate cyclase
has externalized ligand domain, transmembrane domain and and internal catalytic domain
what is soluable guanylate cyclase used for ?
target for some membrane soluable ligands
function of guanylate cyclase ?
when activated , catalytic domain of membrane bound version will GTP into cGMP which will bind to signalling proteins to initiate cell processes
generally speaking the role of protein kinases is to do what?
phosphorylate other proteins that contain serine , theorine and tyrosine residues
what are the 2 classes of protein kinases that act as receptors
Receptor Tyrosine kinases and serine/ Theorine kinases receptors–> will phosphorylate either tyrosine or Theorine
tyrosine kinase receptor bind to ligand cascade of events
1) before binding the inactive receptors are separate polypeptides with inactive tyrosine kinase domains
2) Binding to signalling molecule will cause dimerization – activating the kinase
3) Transautophosphorylation happens when cytoplasmic tail of one subunit is brought close to tyrosine kinase domain of other subunit and opposite domain is phosphorylated
4) resulted phosphotyrosine amino acids are binding sites for signalling proteins to pass signal down the pathway
5) ligand is released and amino acid is dephosphorlayed by phosphoprotein where the kinase will reset to inactive state
parts of a signal transduction pathway
1) either membrane permeable or impermeable receptors
2) signalling proteins and second messengers
3) cytoplasmic receptors
4) sometimes nucleus effectors
2 kinds of protein kinase receptors
1) receptor tyrosine kinases ( RTK)
2) serine/theorine receptor kinases
transmembrane scaffolds
dont always have specific function and will form in large clusters of receptors and signalling proteins
function of transmembrane scaffolds
bring singalling proteins together
regulate signal transduction
send signal proteins to specific cellular area
isolate signalling pathways
nuclear receptors
intracellular receptor that is found in the cytosol of the cell , bund to receptor , ligand such as steroids will move into the nucleus and can bind to steriod response elements that are able to control gene expression
2 common features of all signalling proteins
mobility and catalysis( amplication of signals )
purpose of signalling proteins
to transmit and amplify signals , can mobilize secondary messengers
what are G proteins ?
proteins that bind GTP and propogate signals there are 2 kinds, monomeric and heterotrimeric which differ in the # of polypeptides
4 steps in activated G protein
binding , seperation, propogation and cleave and reform
binding stage of activation of G protein
heterotrimer containing subunits of beta nd gamma are bouND to GDP which is inactive - ligand binds to receptor will change form to interact with heterotrimeric G protein
seperation phase and activation of G protein
exchance of GDP for GTP on the alpha subunit and heterotrimer will seperate in to 3 subunits , G proteins are active
propogation phase in G protein activation
alpha, beta , gamma subunits will bind downstream targets to propogate signal pathway
cleave and reform
Alpha subunit cleave GTP to form GDP which allow the subunits to bind to the hetertrimer again and will bring the protein back into its inactive form
cytosolic protein kinases
can act as intermediaries that can activate other protein kinases and signalling proteins or can phospohorylate effector proteins directly
calcium binding proteins
can cause downstream effects on other proteins ex) calmodulin , Ca levels high, will bind to calmodulin which will activate it causing a conformational change and will bind to its target
adyenyl cyclase
a signalling protein that can bind to the alpha subunit on. hetertrimeric G protein
2 different forms of alpha subunits on Heterotrimeic G protein
as- stimulate adenylyl cyclase where as Ai WILL inhibit it
lipid kinases
signalling protein that will phosphorylate phospholipids in cytoplasmic leaflet - add phosphate group to polar head of phospholipid- also causes conformational change allowing it to bind to target to pass signal
adaptor protein
not a receptor or enzyme , recognize phosphoylated amino acids and can form the glue for signalling networks - so cascades are associated in the right place at the right time
