Bio 1-L14-Conservation of Signalling Pathways between Organisms

what is juxtacrine signalling and an example

notch pathway

• signalling to a cell directly next to the target cell

• Notch-Delta pathway is an example

what does the notch signalling pathway do? what does it involve

• controls cellular identity, differentiation and apoptosis

• it instructs the cells around it to choose a different fate from its own

involves a ligand induced protein cleavage

what are the key things in the notch pathway?

delta type ligand

receptor notch

proteases- furins- cleave the receptor to activate it

CSL transcription factor

notch pathway signalling pathway- and where is it synthesised?

synthesised in the ER and moved to the Golgi

1. notch undergoes proteolytic processing in Golgi-cut by furin(S1)-and moved to the sell surface. e

2. neighbouring cell binds with Delta/Jagged to the Notch-ECD domain- this induces S2 cleavage by ADAM proteases- enodocytosis of Notch extracellular domain

3. S3-S4 is cleaved by gamma protease to release notch intracellular domain

4. now Notch intracellular is active- translocates to nucleus and interacts with CSL protein

5. CSL without notch intracellular- bound to co represor

6. Intracellular notch and CSL along with MAML- make a complex and turn on HESS(for cell growth)

how is the notch signalling pathway turned off

• once target genes hit- notch intracellular is downregulated

• E3 ubiquitin ligase attaches to notch ICD- targets to proteasome

what is a proteasome

a protease complex in cytosol- degrades intracellular proteins

what are cancer treatments that target notch

1. gamma secretes inhibitors- stops the S3/S4 cleavage

2. monoclonal antibodies- stops the binding to Notch ligands

how is protein synthesis regulated?

by TOR kinase- regulates translation and transcription

mammalian mTORC1 structure

• mTORC1 and mTORC2

• mLST8

• raptor

how does protein synthesis controlled by mTORC1

1. mTORC1 phosphorylates key proteins S6K1/2 and 4E-BP1

what do the two key proteins mTORC1 phosphorylates do

• S6K1/2- phosphorylates ribosomal proteins- more synthesis

• 4E-BP1- inhibits key translation initiation - inhibits- when phosphorylated it ALLOWS translation

how is mTORC1 regulated?

• by G protein Rheb- GTP active, GDP inactive

• Rheb is controlled by TSC1/TSC2- inactivates

nutrient sensing and activation of mTORC1

• when insulin is high- AKt inhibits TSC2- ACTIVATE TORC1- energy high

• AMPK from exercise- AMPk turns on TSC2- inactivate TORC1- energy low

what do plants use for nutrient sensing etc?

plants use TORC but instead of SNRK-1

what is the difference between phosphorylation in plants and mammals?

• AMPK in mammals- phsoprylate inhibitory serine

• SNRK-1 phosphorylated inhibitory residue in RAPTOR