Cell Signalling Flashcards
Possible Outcomes of Cell Signalling Events in the Receiving Cell:
Migrate Survive Divide Differentiate Die
Types of Intercellular Signalling
Endocrine Signalling - Hormone signals travel through the bloodstream Paracrine Signalling (A cell produces a signal to induce changes in nearby cells) Autocrine Signalling (Signalling cell and the target cell are the same cell, i.e. induces changes in itself)
Possible means of generating differences between cells:
- Cell-cell signalling or induction: e.g. Diffusion, direct contact, gap junction.
- Asymmetric cell division or segregation of cytoplasmic determinants.
What are the key components of a signalling pathway?
Ligand
Receptor
Transducer
Effector
Differentiation Response is dependent both on the signal received and the competence of the receiving cell.
TRUE OR FALSE
TRUE
Cells signal to the ECM, to cells like themselves and to cells that are different from themselves: the competence to respond to the signal will therefore vary depending on the receiving cell/substrate.
These cell fate choices are the ones that both stem cells and tumorigenic cells make, highlighting the crucial link between developmental biology and disease.
5 Key Developmental Signalling Pathways and Examples of Their Roles.
Hedgehog pathway: bone development, cell fate specification in the spinal cord, limb digits
Notch pathway: cell fate choice, stem cells, gut & heart development, segmentation
Wnt pathway: cell fate specification in the spinal cord, stem cells, gut development
TGFB pathway: bone development
FGF (Fibroblast Growth Factor) pathway: stem cells, limb bud development, segmentation
All 5 are essential during embryonic development .
Aberrant activation of these pathways is observed in a wide variety of cancers.
Note: there is a lot of “cross-talk” between pathways.
How does cell signalling lead to pattern formation in a tissue?
The French Flag Model:
Used to represent the effect of a morphogen on cell differentiation: A morphogen (e.g. Hedgehog) is a molecule that defines two or more cell states at different concentrations.
These states are represented by the different colors of the flag: high concs activate a “blue” gene, lower concs activate a “white” gene, with “red” serving as the default state in cells below the necessary conc threshold.
Cells can obtain positional information via concentration of morphogen (As above) or via “Relay Systems” (measures the different amounts of the same signal vs different signals)
Hedgehog Pathway:
SHH (Sonic HedgeHog) is involved in the separation of the single eye field into two bilateral fields. When SHH is not present, you get cyclopia (One eye).
Ligand: Hedgehog (SHH)
Receptor: Patched
Transducer: Smoothened
Effector: Gli 2 and 3
Hedgehog binds to Patched which relieves repression of Smoothened. Smoothened then represses the proteolysis of Gli. Full length Gli activator goes to the nucleus and activates target gene expression.
Notch pathway
Important for cell-cell communication and neuronal function and development.
Ligand: Delta/Jagged
Receptor: Notch
Transducer: NICD
Effector: RBPjK
RBPjK acts as a transcriptional repressor in the absence of Notch signalling. However, in the presence of Delta/Jagged, Notch is activated and cleaved and NICD goes to the nucleus and together with RBPjK activates target gene expression.
Notch is a cell-cell contact signalling pathway
Wnt Pathway
Activity of the Wnt pathway is involved in the development of benign and malignant breast tumors.
Ligand: Wnt
Receptor: Frizzled/LRP
Transducer: Dishevelled
Effector: Beta-catenin
Inhibited Wnt: B-catenin is phosphorylated by a destruction complex and degraded by the proteasome in the cytoplasm .
Active Wnt: B-catenin is released and free to go to the nucleus and activates target gene expression.
Wnt is both a paracrine and autocrine signal.
FGF Pathway
Involved in angiogenesis (formation of new blood vessels) and wound healing.
Ligand: FGF
Receptor: FGFR
Transducer: ERK/AKT
Effector: ETS
