0
Q
Specialized architecture of auditory hair cells in organ of Corti
A
- ear drum hits the membrane, membrane vibrates and this affects the fluid
1
Q
Cell turnover
A
Some cells are specialized and therefore cannot regenerate if they are damaged (ie. auditory hair cells/photoreceptors
2
Q
Architecture of Ear and Generation of Action Potential
A
sound causes vibration of basilar membrane, which then causes the fluid to move the tectorial membrane
- sound waves cause stereocilia atop hair cells to tilt
- tilt towards tallest: open of ion channels, which creates a nerve impulse
- sound waves are then converted to nerve impulses
3
Q
Mammals and hair cells
A
- cannot regenerate when they are lost
- the loss can be due to diesase, toxins, extreme noise
- other vertebrates can replicate these cells
4
Q
Stereocillia Dynamics at the Molecular Level
A
- stereocilia are filled and supported by actin
- actin continually polarized –> treadmilling
5
Q
Human photoreceptor as a permanent cell type
A
- another type of permanent cell
- photoreceptors convert light waves into nerve impulses
- use a pulse chase experiment
6
Q
Extracellular Turnover: bone
A
extracellular matrix that forms bone is continually digested by osteoclasts and deposited by osteoblasts
- osteoclasts move around, destroying the bone
- osteoblast secrete bone…eventually will be trapped and turns into osteocytes
7
Q
Stem Cell
A
- not terminally differentiated
- can divide without limit
- daughters can remain a stem cell or differentiate
- cell turnover can be dependent on these cells or not
8
Q
Cell Renewal
A
- cell renewal can occur from division of differentiated cells as well (not just step cells)
9
Q
Control of the fates of stem cell daughters
A
- Division Asymmetry
10
Q
Divisional Asymmetry
A
- one daughter receives factors promoting “stemness”, and the other receives factors promoting differentiation
drawback: if stem cells are lost, their original numbers cannot be restored
11
Q
Environmental Asymmetry
A
- cell division is symmetric
- fate determined by the environment
- if stem cells are lost, then their numbers can be increased by having btoh daughters of division enter environment promoting stemness
12
Q
Slow division of stem cells
A
Protects cells from:
- mutations associated with cell division
- Telomere depletion associated with cell division
- there is a committed transit amplifying cell
13
Q
Skin stem cells and their progeny
A
- stem cell reside in basal layer, they require attachment. Basal lamina provides a niche for stem cells
- after detachment: differentiation through a linear sequence of cell types
- without renewal: skin lost for a month
14
Q
Blood Stem Cells and their Progeny: Haematopoiesis
A
- blood stem cells differentiate into various populations creating a branched pathway to a final differentiation
15
Q
Common Lymphoid Progenitor
A
Developed thymus – T cell
B cell
Dendritic Cell
NK cell
16
Q
Common Myeloid progenitor
A
- dendritic cell, neutrophil, monocyte –> macrophage, osteoclast
- eosinophil
- basophil, mast cell
- I) megakaryocyte –> platelets
II) erythrocyte
17
Q
Blood stem cells and their progeny reside in bow marrow
A
A mouse was x-irradiated, which halted blood cell production…without treatment it would die
So you inject bone marrow cells from a healthy donor
- the mouse survives; the injected stem cells colonize its hemopoietic tissues and generate a steady supply of new blood cells
18
Q
Identifying blood stem cells and their progeny
A
homogenize mouse bone marrow to release single cells
expose cells to fluorescent antibodies recognizing specific cell surface molecules
Isolate labelled cells by FACS
basically separate stem cell by charge
garbage is collected in the flask
- a cell has a fluorescent antibody, it is the stem cell so we will give it a negative charge; if not the charge is positive (can see this through laser)
19
Q
Maintenance of Blood Stem Cells
A
- mainted through i/a with stromal cells in bone marrow
- stroma cells provide a niche for the blood stem cells
- if we want a stem cell to stay a stem cell, it MUST be attached to the stromal cell
- Kit binding
- stem cell is attached to stromal cell through Kit…transit amplifying detaches and cell will differentation or die or can stay maintained
20
Q
Stem Cell and Progeny Regulation
A
- for the supply of correct numbers of differentiated cells
Stem cell to committed progenitor:
1. frequency of stem-cell division
2. probability of stem-cell death
3. probability that stem-cell daughter will become a (II)committed progenitor cell of the given type
4. Division cycle time of committed progenitor ccell
5. Probability of progenitor cell death
(III)
6. Number of committed progenitor cell divisions before terminal differentiation
IV)
7. Lifetime of differentiated cells
21
Q
Stem cells and tissue renewal can affect how we age and can treat diseases and disabilities
A
k
22
Q
Medical Uses for Stem cells
A
- can use blood stem cells to treat leukemia
problems of immune rejection - careful tissue matching and immunosuppressive drugs
- if cancer arises from a mutation in one of the progenitor populations, then the patient’s own stem cells can be sued after sporting
- if cancer arises, use electronic sorting technique to collect stem cells again, and destroy all the other cells
23
Q
Can cells of a different tissue be used to make stem cells for treatment?
A
occurs naturally during limb regeneration in newts
- muscle cells de-defferentiate, become mono-nucleated and start dividing
- a bud similar to the embryonic limb bud is formed from the cells
- their progeny form all of the cellt ypes needed to re-grow the limb
24
Embryonic stem cells can proliferate indefinitely in culture and have full developmental function
using all of the factors can change the cells into different cells depending on which factor is used
- icnreases the yield of cells needed for treatment, but ethical issues, immune rejection and the potential of cancer are still concerns
25
Two potential ways to avoid immune rejection of ES cells
1. Somatic cell nuclear transfer - use a nucleus from one of the patient's own cells and transfer it into an unfertilized egg to develop an embryo from which ES cells can be harvested
2. treat some of the patient's own cells with factor known to specify ES cell character
26
Cellular Signalling
- communication necessary to develop and maintain multicellular organisms
- unicellular bacterial-like organisms existed on earth for ~2.5 billion years before complex multicellular organisms arose
- delay may have been due to the time needed to evolve complex signalling systems
27
Examples of unicellular communication
quorum sensing in bacteria
mating in budding yeast
aggregation of ameboid cells
28
quorum sensing in bacteria
- many bacteria release and respond to chemical signals
| - signaling coordinates motility, antibiotic production, spore formation and sex
29
mating budding in yeast
signalling between yeast cells prepares them to mate
30
aggregation of ameboid cells
Signaling between dictyostelium cells draws them together to form a fruiting body
31
Two main ways cells receive signals:
cell surface receptors
intracellular receptors: carried into the cell via a carrier protein and this will then bind to an intracellular receptor protein that can be either in the cytosol or the nucleus
32
Contact-dependent signalling
- short
| - signals are retained on the cell surface
33
paracrine signaling
- signals are released from cell but act locally
signal movement restricted by:
1. internalization by neighbouring cells
2. signal instability or destruction by extracellular enzymes
3. binding to extracellular matrix molecules
- short
34
synaptic signalling
neurons extend axons to contact distant target cells
- released signaling molecules act locally at target
- long
35
endocrine signaling
endocrine cells secrete hormones into the bloodstream for a long-range distribution
- long distances
36
signal transduction
conversion of extracellular signals into intracellular signals
37
effector
downstream molecule in a signal transduction pathway
| - upstream molecules have their effects on them
38
Process
Extracellular signal molecule binds to receptor protein
Intracellular signaling proteins change and produce effector proteins that either: alter metabolism, altered gene expression, altered cell shape or movement
39
second messengers
small intracellular molecules
- made in large numbers and diffuse through the cytoplasm or plasma membrane
- bind and alter effector molecules
40
Large Intracellular molecule
typically proteins
| - organized into pathways and networks
41
Components of signal transduction pathways
```
primary transduction
Relay
Transduce and amplify
Integrate
Spread
Anchor
Modulate
Effector protein activation
```
42
Relay
sends the signal downstream in the same basic form
43
Transduce and amplify
converts the signal into a different form (e.g. an enzyme making a small molecule or phosphorylating downstream proteins)
amplifies the signal by performing many conversions
44
Integrate
Requires inputs from two or more pathways to send the signal on ( a coincidence detector)
45
Spread
sends the signal to other pathways (increases the complexity of the response
46
anchor
restricts the location of the signaling (recruitment to a subcellular compartment)
47
modulate
restricts the intensity of the signaling (down-regulation)
48
addition and removal of phosphate groups on proteins
signal comes in and protein kinase is activated and switches ATP to ADP and a signal out you get protein phosphatase to turn it off
there are serine/threonine kinases and tyrosine kinases (kinases that add phosphatase to tyrosines)
49
GTP or GDP binding
GDP bound - off
signal comes in and GDP switches with GTP - on
signal out via GTP hydrolysis
- GTP-binding proteins are large trimeric and small monomeric types
have low GTPase activity
50
GTPase activating protenis (GAPs)
increase the GTP hydrolysis
51
Guanine nucleotide exchange factor (GEFs)
promote the xchange of GDP for GTP
52
SH2 and PTB binding domains
you have a IRS1 docking protein
SH2 of Grb2 protein binds to IRS and SH3 is bound to a scaffold protein
PTB is bound to the activated receptor
53
Synaptic Signaling Specificity
Nuerons make connections with specific target cells (the same signaling molecules can be used at all connections)
54
Endocrine Signaling Specificity
Different molecules are released and target cells express specific receptors to respond to specific molecules
55
different cells can also have different rsponses to the same molecule by changing the singal receptor or downstream components of the pathway
k
56
What prevents an upstream signal from activating all of the pathways?
the formation of local complexes helps insulate pathways from each other
57
Assembly of signaling complex on an activated receptor
Inactive intracellular signaling proteins when activated bind to the receptor and create downstream signals
58
Assembly of signaling complex on phosphoinositide docking sites
You have an inactive receptor and phosphoinositides and inactive intracellular signalling proteins
when the signal molecule binds, activated receptor
sends signal to phosphoinositides which get hyperphosphorylated and now you have an activated intracellular signalling proteins which create a downstream signal
59
Coincidence detectors
only activate downstream signals when two upstream signals are both detected
ensures two conditions are met before the cell responds
therefore, these downstream signals are very specific
60
Signaling and time friends
synaptic: fast endocrine: slow
response speed to a signal can also be slow or fast depending on the cellular machinery involved
speed with which the cell can turn off signaling depends on the stability molecules involved
BIO230
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