Cell signalling 1 Flashcards
cell signalling basic concept
Chemical signal released by one cell recognised by another
Involves receptor tat recognises signal in specific manner
Allows recipient cell to make a response
Why is cell signalling important
- coordination of cell behaviour
- single cell organisms use signalling to identify and interact with cell of correct mating type in sexual reproduction
- Multicellular organisms depend on cell signalling for correct development, tissue maintenance and homeostasis
Importance of cell signalling in development
Some cellular decisions during development of a multicellular organism are influenced by signalling.
what does mis-regulation of cell signalling in development lead to
cancer
Insulin signalling
insulin signals to tissues (adipose, muscle, liver) promoting storage of energy reserves
Secreted in response to incr blood glucose levels and AAs
Failure of pancreatic B cells (insufficient insulin production) or response of peripheral tissues (insulin sensitivity) leads to diabetes
4 types cell signalling
endocrine, paracrine, neuronal and contact-dependent
Lateral inhibition mediated by the delta-notch signalling system
during development in parts of the nervous system 2 specialised cell types (neurons and support cells) are formed in a organised manner through contact mediated cell signalling involving Delta (signal) and notch (receptor)
Notch receptor can change expression of genes inside the cell
Delta notch signalling more detail
Unspecified cells are equivalent, each cell signaling to its neighbours to maintain low levels of neurogenin (promotes low levels of delta expression)
Some cells will express by chance higher levels of delta. Signals to surrounding cells to prevent neurogenin expression and i) stops them from differentiating as neurones and ii) reduces their expression of delta
Neurogenin levels incr in cells not receiving delta signal - allows expression of factors eg Neuro D, that initiate neuronal differentiation
What is the range of delta signal limited by
its attachment to the cell surface
What other mechanisms could be used to ensure local signals don’t act too far from their origin?
Mechanisms in certain parts of a tissue which breakdown the signal
Signal gets stuck in ECM
What other mechanisms could be used to ensure local signals don’t act too far from their origin?
rapid degradation
Binding to inhibitory proteins
Binding to the ECM
Response to a signal is
cell type specific eg Ach brings out a different response in heart muscle, salivary glands and skeletal muscle
On cardiac and salivary gland cells the receptor is a GPCR, whereas on skeletal muscle its a ligand-gated ion channel
Response to a signal is
cell type specific eg Ach brings out a different response in heart muscle, salivary glands and skeletal muscle
On cardiac and salivary gland cells the receptor is a GPCR, whereas on skeletal muscle its a ligand-gated ion channel
Changes in cell behaviour may results from
integration of many signals
signal-receptor interaction starts
chain of molecular changes inside the cell eg changes in the cytoplasm (altered metabolism or cytoskeleton) and nucleus (altered gene expression)
Intracellular signalling pathway/molecular relay can allow
- Modulation of the signalling pathway, eg cross-talk with other signalling pathways
- amplification of the pathway
- Distribution of the signal to all parts of the cell
relay is from receptor on CSM to eg nucleus, and often involves an en\yme
cell surface receptors
eg GPCRs
, enzyme linked receptors
Intracelllular receptors
act directly as TFs eg steroid and thyroid hormone receptors
or enzymes directly activated by the signal molecule (can cross CSM) eg guanyl cyclase activated by NO
steroid and thyroid hormones
small, hydrophobic signal molecules that interact with intracellular receptors
The hormone-receptor complex acts directly as a TF to regulate expression of specific genes
NO
dissolved gas
acts as a signal
Relax blood vessels to treat angina by relaxing muscle around BVs
Nitric oxide signalling: why is it short lived
rapid and short lived
NO reacts readily with oxygen to form nitrates /nitrites
Half life of 5-10s
ensures local actions
Nitric oxide signalling how does it work
triggering of signalling system begins with release of nt from a nerve terminal which is making contact with the BV endothelial cells
Stimulates production of nitric oxide from arginine in the cell. NO can diffuse across into smooth muscle cells where it acts on its targets- its receptor is guanylyl cyclase (an enzyme), which makes smooth muscle relax and dilates blood vessel
Actions of NO and viagra
Target enzyme for NO, guanylyl cyclase, converts GTP to cGMP
Incr cGMP levels cause smooth muscle relaxation
Signalling reversed when cGMP converted to 5’ GMP linear form by cGMP phosphodiesterase
Viagra inhibits the PDE5 phosphodiesterase and prevents cGMP breakdowm in BVs of the erectile tissue, resulting in sustained/longer signalling response.
shows importance of signal reversal mechanisms and signalling pathways as drug targets
endocrine signalling
Signal produced by gland/endocrine cell. Hormone goes into bloodstream and receptors for that hormone are on the target cells
Long distance, prolonged process
Paracrine signalling
Signal produce by a cell, signal only travels a short distance- acts on cells in same tissue or adjacent tissue
short term
Neuronal signalling
involves 1 cell releasing neurotransmitters that are released across the synapse and detected by receptors on the target cell
Rapid
contact dependent signalling
only communicating to immediate neighbours
Display a signal on the cell surface and have a receptor on the target cell next to it
Signal-receptor interaction is between adjacent cells
What do delta notch signalling allow
cells to be sorted into at least 2 different types eg nerve and epithelial
Where is testosterone (hormone) released from
leydig cells
Androgen insensitivity syndrome
XY individuals who would develop male characteristics but lack receptors for testosterone and develop female characteristics
