Cell biology Theme 2 Flashcards
Why do cells need to communicate ?
To define their position , fate and growth
to function as a community
to respond to the environment
What is the generic cell signal pathway ?
An extracellular signal interacts with a receptor and recieves the signal
the signal is transduced
new intracellular signaling molecules are produced
this leads to a molecular change that alters the cell behaviour
Examples of cell signals ?
cholesterol based steriods peptide hormones fatty acid derivatives amino acids nucleotides
What is endocrine signaling ?
When endocrine cells release hormones that act on distant target cells.
Where are hormones produced ?
in endocrine organs such as the pancreas
How do the hormone molecules reach their target cells ?
`via the blood - a very public system
how do amino acid derivatives and peptide hormones act ?
via receptors on the plasma membrane to regulate metabolism
How do steroid hormones act ?
via intracellular receptors to regulate metabolism
What is endocrine signaling used for ?
respond to nutritional changes , inducing a wide range of changes and in changes to do with development
What is autocrine signaling ?
When a cell secretes a hormone or messenger that binds to autocrine receptors on the same cell that secreted it , leading to changes in that cell
How does autocrine signaling promote cancer ?
In cancer there is an over production of growth factors that lead to the formation of tumours. Due to a disfunctional autocrine signaling pathway
What is lidocaine and how does it work ?
An anaesthetic used to block pain , it moves to the inside of the cell and and binds to sodium channels blocking the influx of sodium ions. This stops nerve conductance and prevents further signals reaching the brain
Why is adrenaline used with lidocaine ?
adrenaline keeps the lidocaine local because lidocaine stimulates dilation of the blood vessels. increasing its absorption. Adrenaline constricts the blood vessels to counteract this
How do cells respond selectively to signals ?
because it depends which receptors the cells have and express
How do different cells respond to the same signal ?
in different ways
Cells having many different receptors allows for what ?
A small number of signaling molecules
Why do signals not act independently of one another ?
the presence of a signal can modify the responses to another signal
What do signals work in to regulate the behaviour of the cell ?
combinations
What can happen to a cell if it is deprived of signals ?
apoptosis
how can cells produce different responses to signals ?
by the interaction of intracellular systems
Why do some extracellular signals have a rapid effect ?
Because they have an effect on a proteins that are already present in the cell
Why do changes cell growth and cell division take hours to execute ?
the response requires changes in gene expression and production of new proteins
What is paracrine signaling ?
A form of cell to cell communication in which a cell produces a signal to induce changes in nearby cells altering the behavior of these cells.
What are common paracrine signaling molecules ?
cytokines and growth factors
What do paracrine signaling molecules act as ?
local mediators
What is the extent of paracrine signaling ?
it is restricted to a particular tissue and is localised eg. the immune response and wound healing
What is neuronal signaling ?
Delivering signals over long distances quickly and specifically to target cells through private lines (axons)
What to electrical signals at the axon terminal stimulate ?
the release of neurotransmitter which diffuses across the synapse eg. Acetylcholine
What do nerve cells communicate between ?
each other or muscle cells
What does acetylcholine do ?
binds to receptors on sodium channels and allows the influx of sodium ions to generate action potentials
What is contact dependent signaling ?
the signaling molecules are membrane bound and they bind to receptors embedded in the plasma membrane , direct physical contact is required
eg in the immune response/
What is delta notch signaling and how is in involved in development ?
Unspecialised epithelial cells form a sheet. An isolated epithelial cell develops into a neurone, inhibition of the rest of the cells must be initiated when the epithelial cell has delta molecules that bind to a notch. inhibiting development into a neuronal cell.
Molecules that are too large and hydrophilic bind to receptors where ?
on the plasma membrane
molecules that are hydrophobic bind to receptors where ?
in the cytosol or nucleus
What are nuclear receptors ?
they are activated by hormone binding which activates them allowing them to promote or inhibiut gene expressions as each hormone binds to different regulatory sets of DNA
The same hormone envokes what types of responses in different target cells ?
envolke different physiological responses
What is an intracellular signaling pathway ?
ann extracellular signal binds to receptors activating a series of intracellular actions that form a pathway
What is the primary step in intracellular signaling pathways ?
the receptor protein carries out signal transduction. the signal activates the receptor, recognises it and generates new intracellular signals in response
What do intracellular pathways usually end in ?
gene expression , enzyme action or cytoskeletal changes for shape change
What is the function of intracellular signaling pathways ?
the relay and transduce the signal
they amplify the signal
they integrate signals from other pathways
they distribute the signal to other intracellular targets
How are pathways subject to positive feedback ?
a downstream component acts on an earlier component to increase the response to the initial signal. this produces an all or none repsonse
How are pathways subject to negative feedback
a downstream component will inhibit an earlier component to diminish the response to the initial signal. this allows the response to oscillate between on and off
What are molecular switches ?
they receive signals which allows them to toggle between on/off
What are the 2 types of molecular switches ?
GTP binding proteins and proteins activated by phosphorylation
How do phosphorylated proteins work ?
Protein kinase adds a phosphate group amde available form ATP hydrolysis.
What does protein phosphatase do ?
removes the phosphate group
What does the activity of a phosphorylated protein depend on ?
the balance between the activities of protein kinase and protein phospohotase
what are phosphorylation cascades ?
when a protein kinase is phosphorylated causing another to be phosphorylated. and a chain reaction occurs. this amplifies the signal.
How do GTP binding proteins toggle between active or inactive ?
if GTP is bound - they are active
if GDP is bound- they are inactive
GTPase activity regulates this
What are the 3 types of extracellular receptors ?
ion channel linked receptors
g-protein linked receptors
enzyme-linked receptors
What do ion channel linked receptors do ?
they change the permeability of the plasma membrane to selected ions , altering the membrane potential.
What is the structure of a G protein coupled receptor ?
It is a single polypeptide chain that threads back and forth across the membrane 7 times, this is the seven-pass transmembrane structure.
What happens when an extracellular signal binds to a G-protein coupled receptor ?
when the signal binds to its receptor the altered receptor activates the G protein as the GDP is removed and the GTP is bound,
What do G-proteins often interact with ?
enzymes- adenylyl cyclase that produces cyclic AMP and phospholpiase which makes inositol triphosphate and diacylgylcerol.
What are cyclic ACP, IP^3 and DAG ?.
second messengers - they amplify and spread the signal
What are the consequences of GCPR activation ?
activation of membrane bound enzymes (adenylyl cyclase)
activation of phospholipase C ( makes DAG and IP^3)
regulation of ion channels (eg. potassium channels)
How do GPCR regulate ion channels ?
acetylcholine binds to receptor - this activates the G protein
This allows the potassium channels to open and membrane permeability increases
The G protein is inactivated as the GTP is hydrolysed
the potassium ion channel closes
What is the ‘flight or fight’ response ?
Adrenaline binds to the GPCR
this activates the adenylyl cyclase
the production of cAMP is amplified
this activates protein kinase A and leads to cascades
phosphorylation of phosphorylase kinase
this activates glycogen phosphorylase which breaks down glycogen into glucose
How can cAMP modify gene expression ?
a signal binds to a GCPR
this leads to an increase in the activation of adenylyl cyclase
this leads to an increase in cAMP which activates protein kinase A
this moves into the nucleus and phosphorylates specific transcription factors
How do enzyme coupled receptors work ?
an extracellular signal binds to the receptor and enzyme activity is activated within the cell
they are usually in pathways that control growth,development and differentiation.
slow responses as changes are required to gene expression.
what is the central dogma of molecular biology ?
transcription and translation
Why is it useful for a cell to make multiple copies of mRNA ?
to allow successive amplification so that cells can rapidly synthesise large amount of desired protein
what do different rates of transcription and translation provide ?
a way of making different quantities of protein as different cells require different amount of proteins
what is the process of transcription ?
RNA polymerase latches onto a region called the promoter
it opens the double helix
one strand acts as the template
complementary base pairing with RNTPs
a terminator is reached
phosphodiester bonds are made and energy comes from hydrolysis of phosphate bonds
What are some differences between RNA and DNA ?
there is no hydrogen bonding in RNA therefore its single stranded
RNA is short because it is made from a limited region of DNA
RNA is not a permanent storage of information , DNA is
The RNA synthesised complementary to ?
the template strand
the RNA is identical to ?
the coding strand
In prokaryotes the RNA transcript has how many genes in it ?
multiple functionally related genes
In eukaryotes how many genes does the transcript have ?
1
Do prokaryotes have promoter regions ?
no
what steps must mRNA go through before it can be translated ?
capping
splicing
polyadenylation
What is capping ?
modifying the 5’ end of RNA and adding a nucleotide derivative which makes the RNA more stable and allows transport into the cytosol.
What is poladenylation ?
the 3’ end is trimmed by an enzyme and repalced with a tail of repeated A nucleotides. This allows for the molecule to be identified as mRNA.
What is RNA splicing ?
Introns are removed and exons are stitched back together
A few nucleotides in the intron cue for their removal
What is alternative splicing ?
Transcripts are spliced in different ways each proding a different protein called an isoform. this allows us to have an extensive genome
nuclear pores act as what ?
gateways
transport to the cytosol is ?
highly selective
Which mRNAs are transported out through the nuclear pore ?
ones with an adenylyl tail , a 5’ cap and proteins that are only present after splicin
What happens to waste mRNAs
they remain in the nucleus and are degraded , recycled for transcription
Why is it important to to regulate the lifetime of mRNA ?
Proteins are required in different amounts , proteins needed in high amounts need a long lifetime whilst proteins produced in response to signals have a short lifetime.
How are mRNA lifetimes controlled
the 3’ untranslated region which lies between the 3’ end of the coding strand and the poly A tail.
what is rRNA important for ?
ribosomal structure and catalytic activity
what does miRNA do ?
regulates gene expression
What is the mechanism of action of miRNAs ?
miRNA are short non coding RNAs
they bind to the 3’ end of the untranslated region of target mRNAs and repress protein production by destabilising the mRNA and silencing it.
How many possible codons are there ?
64
there are 64 possible codons , but only 20 amino acids what does this suggest ?
a redundancy in the code ?
How many different stop codons are there ?
3
How is the genetic code universal ?
a codon codes for the same amino acid in any organism
An mRNA sequence can be translated in how many different reading frames ?
3
How is the start of the translatory sequence identified ?
an AUG codon - a start codon which determines the correct reading sequence
What shape is tRNA ?
a clover leaf shape
What are the 2 unpaired nucleotide regions on a tRNA molecule ?
the anticodon and the amino acid binding site
The redundancy of the code implies what about the number of tRNA molecules ?
there are more tRNA molecules than the number of amino acids ?
What is the concept of wobble ?
some tRNA molecules are consttructed so they only require accurate base pairing in the first 2 nucleotides , they can tolerate a mismatch (wobble) on the third nucleotide
What is a ribosome ?
a large complex made of more than 80 proteins and 4 different ribosomal RNAs. the large and small sub unit fit together to form the ribosome
What is the function of the small subunit ?`
it matches the tRNAs to the codons on the mRNA
What is the function of the large sub unit ?
catalyses the formation of the peptide bonds between the amino acids
Describe the process of translation ?
Translation initiation factors bind at the 5’ and 3’ ends
small sub unit binds to the 5’ cap
small sub unit shuffles along the mRNA to identify the AUG
tRNA for AUG brings methionine
large sub unit binds and translation can begin
the small sub init shuffles to the next codon
tRNA binds
large sub unit catalyses the formation of new peptie bonds
why are ribosomes described as ribozymes ?
the ribosome has enzymatic properties
as it catalyses the formation of new peptide bonds (large)
also releases the tRNA from the mRNA when the peptide bond is made
How do antibiotics against prokaryotes work ?
they work by inhibiting bacterial protein synthesis
by exploiting small differences in structure and function
What modifications do polypeptides go under after translation ?
post translational modification
covalent modification eg. phosphorylation
binding of small co-factors
Association with other sub units needed for functionality
Why is glycolysation needed ?
some proteins do not fold properly unless they are glycolysed
Why is phosphorylation needed ?
to allow proteins to repsond to extacellular stimuli
Where does protein modification take place ?
ER and golgi
What is the role of chaperone proteins ?
they bind to polypeptides and guide correct folding
How is the final destination of a protein determined and where can it go ?
the intracellular location is determined by an amino acid sequence in the polypeptide
locations include the ER membrane , the lumen of the ER or an organelle such as a golgi vesicle
Degradation of proteins allows for what ?
regulation of the amount of a particular protein
What are enzymes that break down proteins called ?
proteases
What do proteases do ?
destroy proteins with a short lifetime
destroy those that are damaged or misfolded
what are the protein complexes called responsible for degradation ?
proteasomes
How are proteins identified that they need to be destoroyed ?
they are labelled with ubiquitin
proteins with short lifetimes have amino acid sequences that identify them as needing to be ubiquilayted
What can specialised cells do in response to extracellular stimuli ?
alter their gene expression
At the start of transcription what does RNA polymerase bind to ?
a promoter
What do promoter regions contain ?
a transcription initiation site
a sequence of upstream nucleotides that are required for RNA polymerase to recognise the promoter
What do genes have that enables them to be switched on/off
regulatory DNA sequences
What do regulatory sequences act as ?
microprocessors - they integrate signals to dictate how often transcription is initiated
Where are promoters located relative to the gene ?
upstream of the gene
Where do transcription factors bind and why ?
they bind to the promoter and this helps to position the RNA polymerase
Where is a common site that transcription factors will bind to ?
the TATA box , lots of transcription factors will bind formin the transcription initiation complex.
how is RNA polymerase activated ?
phosphorylation
What also binds to the initiation complex ?
proteins
What are enhancers ?
DNA sites that activator proteins will bind to and enhance transcription even thousands of base pairs away
What do the actiivator proteins create ?
they create the correct environment for RNA polymerase II to assemble and form the initiation complex
What can repressor proteins do ?
they repress the formation of the transcription initiation complex
What can transcription regulators also do ?
alter chromatin structure by attracting proteins
this increases the accessibility of transcription factors and RNA polymerase to the promoter
How can nucleosomes inhibit transcription ?
they sit directly on top of the promoters and block assembly of the transcription factors and the RNA polymerase
What are chromatin remodelling complexes ?
they allow chromatin structure to be modified
How does histone modification promote transcription ?
Enzymes can covalently modify histone proteins in the nucleosome
acetyl transferase promotes attachment of acetyl groups to lysine in histones
this alters chromatin structure
allows greater accessibility to DN
the acetyl groups also attract transcription factors
How can acetyl groups be removed ?
histone deacetylases
what is a leucine zipper ?
a transcription factor that binds to phosphate groups in the backbone of DNA and interacts with specific base pairs in the major groove
What must be remembered by a cell once it differentiates ?
changes in gene expression - often triggered by a transient signal must be remembered by a cell
transcription regulators usually work as part of what ?
a committee - all are necessary to express a gene dthe right conditions , at the right time and in the required amount
What is the concept of combinatorial control ?
groups of transcription regulators work together to determine the expression of a gene
Are transcription factors specific for a gene ?
no - some are activators some are repressors
What do transcription factors do ?
they can- assemble chromatin remodelling complexes attract histone modifying enzymes assemble RNA polymerase attract general transcription factors
What is an operon ?
Bacteria coordinate expression of a set of genes by having them clustered together in an operon - under the control of a single promoter
Even though in eukaryotes the control of gene expression is combinatorial what is the effect of a single transcription factor ?
the effect of a single transcription factor can still be decisive in switching a gene on/off
the single TF completes the combination needed to activate transcription
What is the effect of a cortisol receptor complex ?
some proteins bind to DNA sequences but they aren’t enough to stimulate transcription
adding a cortisol receptor complex can complete the combination of transcription factors needed to initiate transcription.
cortisol works by binding to a receptor to create TF
adding the genes of TF to cells can have what effect ?
they can induce cells to generate different cell types
the gene for TF MyoD is introduced to fibroblasts
the fibroblasts from muscle like cells
this is because the fibroblasts possessed the relevant TFs already and the addition of the MyoD completed the unique combination
How can specialised cells be reprogrammed into iPS cells ?
they can coax various differentiated cells into pluripotent cells - used in treatment and research
Why is the property of cell memory needed ?
for a cell to maintain its identity as it proliferates - the specific patterns of gene expression must be remembered and passed onto the progeny
What are the 2 mechanisms for ensuring cell memory ?
epigenetics and positive feedback loops
How does the positive feedback loop work to maintain cell identity ?
master TF activates transcription of its own gene and other cell specific genes
each time the cell divides the TF is distributed to the progeny and feedback is initiated
How do epigenetics work to maintain cell identity ?
DNA methylation of cytosine bases
this turns off genes by attracting proteins that block transcription
DNA methylation patterns are passed onto a progeny by an enzyme that copies these patterns
Modification of histones - inherited histone proteins have covalent modifications that can be conferred to nearby histones to re-establish the pattern of chromatin structure.
What are homeotic genes ?
genes that regulate the development of anatomical structures in various organisms - they supply positional information
What do homeotic genes encode ?
TFs
they are evolutionary highly conserved
What can homeotic genes activate ?`
cascades of other regulators (TF and signaling molecules) and initiate feedback loops
Which molecules are important in developmental regulation ?
TFs
Extracellular signaling molecules
Receptors for signals
Which enzyme is activated in response to gorwth factor signalling ?
tyrosine kinase
what does a Hox gene mutation cause
abnormalities of limb development e.g. synopolydactly
what does a Pax gene mutation cause
developmental disorders of teeth, eye, kidney, skin e.g. waardenburgs syndrome and hypodontia
what does a Msx gene mutation cause
craniofacial and dental disorders e.g. craniosynostosis syndromes and hypodontia
