Colm Cunningham - cell to cell communication Flashcards
what is quorum sensing?
Quorum sensing is a phenomenon in which microbial cells interact and communicate with each other by secreting some chemical molecules to which other cells. remember the bobtail squid and the vibrio fisheri
singling molecule
AUTOINDUCER used for vibrio fisherciheri
Acyl-Homoserine Lactone
cell-cell signalling
-Molecule released by cell
– Both that cell and other local cells can respond
– Via receptor-mediated signalling
– Concluding with activation of transcription factors
– Changes in gene expression, change in cell
behaviour
Juxtracrine signalling is an example of….
contact dependent signalling
outline gap- junctions
the pacemaker cells in the heart or the cardiac myosites must contract together via the passage of ions. Gap junctions or connections in cytoplasm allow for this.
Intercalated discs are points
are which 2 cardiomyocytes are joined part and they contain two structures important in cardiac muscle contraction: gap junctions and
desmosomes.
The function is called
electric coupling
where dos the signal for the pacematers beginning where?
begins with the pacemaker cells IN THE SINO-ATRIAL NODE
what drives the pumping of the pacemaker cells?
Sodium channels, then calcium channels, THEN potassium channels – so we depolarise, then further, then with K we reploarise. All are voltage gated so open AND close according to the voltage so it constantly cycles (never at resting potential). The myocyte (cardiac muscle) is quite different –
as depolarisation starts and calcium wants to come in and potassium wants to move out, they work sort of in opposition the membrane potential plateaus a little
above neutral.
Plasmodesmata:
ER extension – desmotubule
Cytoplasmic sleeve (around tubule)
What molecules move between cells through the plasmodesmata?
Proteins, mRNAs and gene silencing signals use these channels for movement
plasmodesmata
interconnections convey molecules ‘away from’ the
veins.
notch signalling can do what
alter metabolism
alter cytoskeleton
alter gene expression
Endocrine signalling
the signaling molecules (hormones) are secreted by specialized endocrine cells and carried through the circulation to act on target cells at distant body sites
Paracrine signalling
eg the synapse
Autocrine signalling example
cell to itself eg T cell cytokine interleukin-2 (IL-2)
give 2 examples of paracrine signalling
Cytokines released by immune
cells act on multiple populations
Morphogens released to drive
patterning during development
Neurotransmitters released
locally act on multiple target
give an example of a morphogen
WNT protiens form as morphogens causing a secretion gradient
what are the steps of WNT signalling pathway
The signalling
molecule Wnt binds
to the frizzled
receptor.
β-catenin
plays a
central role
No transcription
2. In the case of
stimulation of the
canonical pathway
(there are other
possible outcomes),
ß-catenin is
stabilised in the
cytoplasm
3. is transported to
the nucleus
4. where it binds to
the transcription
factor Tcf and turns
on gene expression.
Neuromuscular junction – acetylcholine (Ach)
na+ inflow, k+ outflow
depolarisation of end plate
Gorge Palade
leucine is labelled radioactively and thus is built into the cell’s protein pulse chance phase also identified
types of chaperones
Calnexin & calreticulin – chaperones that retain
incompletely folded proteins in the ER-THEY CAN’T LEAVE ER UNTIL FOLDING IS COMPLETE
what is a obliglucccharide
a saccharide polymer containing a small number (typically three to ten) of monosaccharides (simple sugars)
which amino acid is added in protein folding
asparagine
how big are er transport vesicles
ER transport vesicles ~50 nm
where do they merge and what coat do they have?
cis-golgi network
cop II coat
what does proinsulin mature into
insulin and c-peptide
what type of folding does preproinsulin undergo?
disulphide bonding
what cuts preproinsulin
endopeptidase
where does this cleavage occur?
in the secretory vesicles
synaptotagmins
were proposed to function as calcium sensors in the regulation of neurotransmitter release and hormone secretion
Zn2+
is essential for the correct processing, storage, secretion, and action of insulin condensation
name one type of vesicle
Dense core granules
name two types of neurons( point is that there are many)
granule cell, spindle shaped cell
what structures are important ofneurotransmitters
cell, axon, synapse
Neurotransmission is
is the conversion of an electrical signal
to a chemical signal, that allows the signal to pass from one
cell to the next
Otto Loewi - what did he do?
proves the existence of acetyl choline by using frog hearts in synapse vagus nerves connection is key to this experiment acetylcholine
types of neurotransmitter
Biogenic amines – dopamine, noradrenaline, serotonin
Amino acid neurotransmitters – glutamate, GABA
Other types – Acetylcholine, NO, D-serine, neuropeptides
Glutamate and GABA
Major Excitatory, inhibitory Neurotransmitters respectively
Catecholamine biosynthesis: dopamine and noradrenaline
form tyrosine to dopa to dopamine to noradrenaline
what enzymes are required for this synthesis
thyrosine hydroxylase, dopa decarboxylase,dopamine b-hydroxylase
where are amine transmitters located?
Amine neurotransmitters are synthesised enymatically in the
cytosol and then packaged into vesicles in the synaptic terminal
what 2 key proteins on small synaptic vesicle
They are specialised in their expression of 2 key proteins
- a vesicular neurotransmitter transporter
- a vesicular ATPase, which pumps H+ into the lumen.
what does atp synthesis require
Vesicular ATPase: pumps H+
into vesicle against
concentration gradient and
therefore requires ATP
hydrolysis,
vesicular neurotransmitter
transporter: transports NT into
vesicle against concentration
gradient
what are vmats and what are their inhibitors?
the vesicular monoamine transporter (VMAT) is a transport protein integrated into the membranes of synaptic vesicles of presynaptic neurons. It transports monoamine neurotransmitters – such as dopamine, serotonin, norepinephrine, epinephrine, and histamine – into the vesicles inhibitors= Tetrabenazine: treatment for
hyperkinesia
Reserpine: antipsychotic
what two signalling are calcium dependent?
paracrine, endocrine
during resting membrane potential what side is positive and which is negative?
extracellular side pos
cytoplasmic side- negative
in these terms what is charge sepration?
Charge separation! The charge on each side is highly ‘regulated’ but it is not balanced
how does a synaptic channel open
ligand ie neurotransmitter causes channel to open
depolarisation does what?
Depolarisation does make the
membrane potential LESS NEGATIVE, but must cross threshold to trigger AP: “all or none
action potential happens how?
1.ligand- gated na+ channels depolarise membrane
2.voltage gated na+ channels depolarize further.
endplate potential happens where?
when a neuron synapses on a muscle cell
axon potential
na+ into the cell,
k+ out of the cell
what are their relative amounts
High extracellular Na+
(440mM vx 50)
High intracellular K+
(400mM vs 20)
what is the difference between ca+ and na+
Na+ is the electrical trigger for depolarisation
Ca2+ is the chemical signal for neurotransmitter release
what is the docking cycle ?
1.Docking of a subset of
these at AZ
2.Priming (for Ca2+-
dependent exocytosis
3. Ca2+ triggering of fusion
pore opening)
4. Recycling
what is the difference between t and v snare
v snares are on the vesicle
t snares are on the target membrane
what are the 3 types of snares?
synaptobrevin
syntaxin-1
snap- 25
what forms the snare complexes?
munc 18
LCs are zinc-dependent endopeptidases, function
which specifically cleave neuronal SNARE
name two toxins and what they work on-
Botulinum toxin (ACh),
Tetanus toxin (GABA)
what is Synaptotagmin
sensor of calcium/ receptor- removes complexin allowing the complex to open.
how can these highly used neurtoransmitters be recycled?
use of a clathrin coat
kiss and run model- only partial emptying of the vesicle
ultra falst endcytosis
AXON HILLOCK
Voltage-gated sodium channels (depolarisation)
INITIATE ACTION POTENTIAL if crossing threshold
Voltage-gated potassium channels
- Repolarisation
AXON
- Propagation of action potential
Voltage-gated potassium channels and sodium channels - Repolarisation, prevention of back propagation
dendrites
collect electrical signal
ionotropic
ligand gated ion channels
direct neurotransmitters binding opening
metrotropic receptors
g coupled receptors
indirect activation through the use of g-protein. slower mode of action.
receptor classes?
nicotinic , Muscarinic
nicotinic
activated by nicotine
ionotropic
Muscarinic
activated by muscarine
metabotropic
Muscle-type Nicotinic acetylcholine receptors
found at the neuromuscular junction (NMJ) role in contractile muscle also a Pentamer with 2 ACh binding sites
Nicotine Acetylcholine receptor pentamer subunits are made out of what?
M1,M2,M3,M4 subunits
Myasthenia Gravis (MG)
It occurs when the immune system attacks nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction (NMJ), preventing proper muscle activation.
Glutamate receptors ionoconic
AMPA, KAINATE, NMDA
(all glutamate analogs)
Mg block/depolarization req.
metabonic glutamate receptors
mGluRs: mGluR1-mGluR8
GABAA receptors
Inhibitory effects,Pentameric structure
inhibitors of Glutamate
Anticonvulsants:
-Block Na+ channels
-GABA agonists open
Cl- channels - hyperpol
