lecture 1 Flashcards
what signalling defects cause diabetes
signalling of hormone insulin
what signalling defects cause cancer
mutations by signalling pathways controlling growth and division
what signalling defects cause inflam diseases
signalling defects of the immune system
what drugs target cell signalling pathways
drugs to targt g protein coupled receptors
target protein kinases
growth and metabolic activity differences in unicellular and multicellular organisms
unicellular organisms a re capable of all their own necessary functions, growth is usually exponential when nutrients are available
multicellular organisms have specialised cells to carry out various necessary functions, growth must be restricted as nutrients are always available exponential growth would lead to cancers. movement must be coordinated throughout cells by the nervous system. during starvation fatty acids are used to provide energy. adipose tissue have an abundant store of triacylgylcerol cells to signal when energy is needed
3 cell to cell methods
cytoplasmic bridges, anchored messenger and secreted messenger
what are direct cytoplasmic bridges also called
gap junctions
how do direct cytoplasmic bridges work
small molecules can pass between neighbouring cells
in mammals these connections are called gap junctions or tight junctions
consist of hexagonal connexons, there are 6 connexins in a connexon around a central pore
how is the pore in jap junctions controlled
at low calcium levels the pore is open and at high calcium the pore is closed
cellular calcium is generally high so this mechanism could be to stop cell content leaking out until cell-cell contact has been achieved
the structure of a gap junction
6 connexins make up a connexon with a central pore
each connexin has 4 transmembrane alpha helices
connexons from adjacent cells join to form full channels, the central pore is approx 1.4nm in diameter
studied through xray crystallography
are gap junctions the functional pore between cells?
the use of electrodes shows electrical current flows between neighbouring cells shows that the pores allow flow of ions
microinjection of fluorescent dye into one cell showed diffusion into neighbouring cells so uncharged molecules can also pass through pores
molecules of up to 1500 Da can pass through indicates they move through the pore as could pass through the 1.4 diameter
pores can allow passage of small peptides, glucose, nucleotides and amino acids
neighbouring cells can share nutrients and be electrically coupled eg. contractile heart cells
how can cultured cells have their gap junctions removed
trypsin can detach and separate neighbouring cells
when trypsin is removed from the culture, gap junctions are reformed
how do anchored messenger cell junctions work
cells signal by messengers to neighbours, the messengers are integral proteins in the plasma membrane
example: compound eye in drosophila
each eye facet contains 8 different photoreceptor cells which respond to diff wavelengths of light
R7 only develops if there is a signal from R8 which is sensed by a sevenless receptor
mut in sevenless gene casues no R7 cells
ligand for this receptor is a sevenspan membrane protein embedded in the plasma membrane of R8
ephrins are membrane proteins that bind to ephrin receptors on nerve cells to guide their axons to the correct target
what are the 3 different types and why do they exist
there are 3 different for different distances, hormones neurotransmitters and local mediators
(most wide spread and familiar cell to cell signalling)
how do hormone secreted messengers work
hormones are relseased by specialised endocrine cells
they secrete molecules to the inside of the organism
they are carried by the blood stream to the target cell
how do neurotransmitter secreted messengers work
nerve cells (neurones) communicate to target cells by secreting messenger molecules called neurotransmitters neurotransmitters are secreted from the nerve terminal into the synaptic cleft - the narrow gap between neurone and target cell axons allow the messenger to be released exactly next to the target rather than transport via the bloodstream communication by nerves is much faster than hormones as the signal travels electrically along the axon
what are local mediators
they are released from the cell to extracellular fluid and only affect immediate neighbours
cells are not specialised, all cells probably secrete loacal mediators
the release is not directional
they are not in significant conc in the blood stream either becasue they bind tightly to the ECM or they are rapidly taken up and broken down by neighbouring cells
this is sometimes called paracrine regulation
example of a local mediator NERVE GROWTH FACTOR (NGF)
1st example was neurotrophin, it acts in the peripheral nervous system
related neurotrophins act on neurones of the CNS
neurotrophins are released by target cells that require innervation by a neurone
neurotrophins are chemotatic - axons grow along concs of increasing neurotrophin concs
axons eventually reach target cells where they form synapses (ones that dont form synapses with approp target cells die)
neurotrophins could not fulfill this axonal guidance function if they were released into the blood stream as their locally acting nature is fundamental to their function
example of local mediator PLATELET DERIVED GROWTH FACTOR (PDGF)
released by platelets which are responsible for the clotting of blood after injury
this stimulates the migration of fibroblasts to the wound and their proliferation
fibroblasts then secrete ECM components like collagen to which other cells attach and repair the wound
localised action of PDGF is crucial, if circulated in the blood fibroblasts would divide everywhere and cause cancer
it its retained locally b y its tight binding to the ECM
