Lecture 7 - Regulation of slow cellular events (division, growth, differentiation and death) Flashcards
The growth and development of an organism depends on:
The growth and development of an organism depends on:
Cell division
Cell growth and differentiation
Cell death
Each of the above is controlled by the activation of specific receptors
TIssue growth in adults
Tissues and organs within an organism also grow
Most retain their final adult size through a regulated balance of cell division and cell death
Cell replacement can become inadequate to balance high rates of cell death (liver cirrhosis)
Lots of dead hepatocytes, dying so fast that they cannot be replaced, other cells instead of hepatocytes such as fat cells grow and this therefore causes fatty liver
Excessive unregulated cell division lies at the centre of tumour formation and cancer
Cell cycle
Cell division and thus cell multiplication occurs via the cell cycle
Divided into 4 phases
G1 = Cell growth
S = DNA duplication (in preparation for the formation of a new cell)
G2 = preparing for division
M = mitosis and cytokinesis (actual cell division (prophase, metaphase, anaphase, telophase, cytokinesis)
G1, S, G2 = interphase
Importance of cell cycle checkpoints
The cell cycle is tightly controlled by a series of checkpoints otherwise could get tumours which can lead to cancer, many cancers are due to defects in the genes that control the checkpoints of the cell cycle
Cell cycle checkpoints are surveillance mechanisms that monitor the order, integrity, and fidelity of the major events of the cell cycle. These include growth to the appropriate cell size, the replication and integrity of the chromosomes, and their accurate segregation at mitosis.
Cell cycle checkpoints list
G1 or restriction checkpoint
G2/M checkpoint
M phase check point
G1 or restriction checkpoint
G1 or the restriction checkpoint requires a mitogenic signal
Are the internal and external environments favourable for division e.g. enough energy and resources?
G2/M checkpoint
G2/M checkpoint controls progression of mitosis
Has the DNA been fully and accurately copied?
M phase check point
M phase check point controls progression to cytokinesis
Are the daughter chromosomes correctly aligned at anaphase?
This checkpoint occurs at anaphase
Checks that chromosomes are lined up properly to ensure that you get a full set of chromosomes
How do checkpoints work in the cell cycle?
Crossing a checkpoint is controlled by a family of protein kinases
Activity of these kinases is regulated by a number of small proteins called cyclins
Hence these kinases are called cyclin-dependent protein kinases (Cdks)
There are multiple Cdks but in essence the cell cycle is controlled by increasing or decreasing the level of specific cyclins
Mitogen work by increasing the level of G1-cyclins
Terminally differeated
Once enough cells have been generated, division slows down and many cells enter a non-dividing stage called G0
In G0 cells turn off genes for division and turn on genes for function
They become terminally differentiated to form the functioning cells of the body (somatic cells)
Terminally differentiated - differentiated as they change shape, terminally as this is their final shape
Terminally differentiated = the course of acquiring specialized functions, has irreversibly lost its ability to proliferate.
Cell loss must still be balanced by cell replacement in adult tissue even with terminal differentiation
But cell loss must still be balanced by cell replacement in adult tissue
This may occur via stem cells (job of a stem cell is to not terminally differentiate)
Stem cells retain the ability to divide when activated by a mitogen
The two daughter cells are different - stem cells do not divide evenly as one goes on to form a differentiated cell with a specific function and the other goes back and replaces the stem cell to ensure that there is always one there
One remains a stem cell (to retain the stem cell pool)
The other differentiates to renew tissue
Stem cells are being extensively explored for tissue/organ replacement treatments
May be possible to reprogram differentiated somatic cells to create induced stem cells
Unipotent
Stem cells may be unipotent - form only one type of differentiated cell such as the skin
Pluripotent
pluripotent - potential to form a number of differentiated cell types as with haemopoeitic stem cell
Action of mitogens
A mitogen is a peptide or small protein that induces a cell to begin cell division: mitosis.
Mitogens act via specific receptors to activate the MAP-kinase signalling pathway
Increases expression of G1-cyclins
These cyclins then activate the G1 cyclin-dependent kinase
Allows cells to pass G1 checkpoint
MAP kinase acts as an activator of transcription factors, it turns on or off genes that are related to cyclins
MAP kinase is also called ERK, activation of ERK leads to the production of cyclin
Some mitogens target multiple cell-types e.g. platelet-derived growth factor (PDGF) or Epidermal growth factor (EGF)
Others are more specific e.g. erythropoietin, EPO stimulates RBC production
Note: name ‘mitogen’ can be confusing because many have growth and differentiation actions as well as stimulating cell division
Action of growth factors
Cell division must be accompanied by cell growth
Mediated by growth factors which activate specific cell surface receptors (G1 phase is mediated by growth factors such as growth hormone)
Increase the rate of protein synthesis, nutrient uptake, ATP production (last two in the list need to occur in order to increase protein synthesis)
Many cells including muscle cells and neurons continue to grow extensively after withdrawal from the cell cycle (i.e. during G0)
Cell growth also regulated by inhibitory factors such as myostatin in muscle
Loss of myostatin results in excessive muscle growth
