Signaling text book summary

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From Molecular Biology of the Cell - Cell Communication Chapter


Contact-dependent signaling

development and immune system p833

local mediators (paracrine signaling)

p834

  • signals don't travel far
  • soon taken up
  • rapidly destroyed
  • immobilised

long distance signals - nervous system

p834

  • nerve cell - electric impulses (action potentials) fast (up to 100m/s)
  • neurotransmitters
  • chemical synapses

see chapter 11 for synaptic signaling processes.

Long distance signals - hormones for endocrine cells

  • transported via the bloodstream
  • slow acting

low concentration -> large effects.


Autocrine signaling

  • Cell secretes a signal that can bind back to its own receptors or those of the same cell type.
  • For example in development this is used to maintain cell identity after initial differentiation.
  • Also used to make sure all adjacent cells differentiate in the same way.

Gap junctions

  • Allows cell to communicate with each other by having a tunnel across the plasma membrane
  • Dye can squirt through the tunnels and this is how people spot them experimentally.
  • Patterns of making and breaking gap junctions are important in development.

Nitrous Oxide

  • NO and CO and other similar small hydrophobic molecules are able to pass straight through the membrane and are used as signals.
  • These bind to intracellular receptor proteins.
  • e.g. steroid hormones, thyroid hormones, retinoids, vitamin D.
  • The signal molecules bind to the receptor molecules, which then become activated, and are able to bind to DNA to regulate transcription.
  • The receptors are all members of the nuclear receptor super family.
  • This leads to the primary and secondary response:


Signaling to control gene expression - Primary response

  • ligands bound by hormones bing to gene regulatory bits and turn on expression.
  • This takes about 30 minutes

Signaling to control gene expression - Secondary response

  • Protein products made in the primary response activate other genes to produce a delayed secondary response.

N.B. This means that a simple hormonal trigger can produce a very complex pattern of gene expression.

Cell surface receptor proteins

3 kinds:

1) Ion-channel linked cell surfacce receptor proteins

N.B. these are the transmitter-gated ion channels that were updated in the transport overhaul. The top level term is already in place. p842

2) G-Protein linked cell surface receptor proteins

3) Enzyme linked cell surface receptor proteins

  • Mostly to do with the protein kinases.
  • Ligand-binding enables phosphorylation of specific proteins in target cell.


First Messengers

These are extracellular signals p843

Second messengers

  • These are small intercellular signaling molecules
  • They diffuse to membrane or cytosol depending on solubility.

Large intracellular signaling proteins

several types:

1. Relay proteins

These simply pass the message to the next signaling component in the chain.

2. Messenger proteins

These carry the signal from one part of the cell to another, such as from the cytosol to the nucleus.

3. Adaptor proteins

These link one signaling protein to another, without themselves conveying a signal.

4. Amplifier proteins

These are usually either enzymes or ion channels, greatly increase the signal they receive, either by producing large amounts of small intracellular mediators or by activating large numbers of downstream intracellular signaling proteins. When there are multiple amplification steps in a relay chain, the chain is often referred to as a signaling cascade.

5. Transducer proteins

These convert the signal into a different form. The enzyme that makes cyclic AMP is an example: it both converts the signal and amplifies it, thus acting as both a transducer and an amplifier.

6. Bifurcation proteins

These spread the signal from one signaling pathway to another.

7. Integrator proteins

These receive signals from two or more signaling pathways and integrate them before relaying a signal onward.

8. Latent gene regulatory proteins

These are activated at the cell surface by activated receptors and then migrate to the nucleus to stimulate gene transcription.


Some Intracellular signaling proteins behave like molecular switches

2 classes:

Both use gain or loss of a phosphate group to determine if a protein is active or inactive.

Proteins activated or inactivated by phosphorylation

p845


       protein kinase ---------->
       (adds phosphate group)

       <-------------protein phosphatase
                     (remove phosphate groups)




Some general features in signaling

  • Cells are bathed in hundreds of different signals all the time.
  • response of different cells to the same signal can be depend on the internal machinery, even if the receptor is the same.
  • some effects on cell are permanent due to cell memory - though this is usually not the case. (chap 7 + 21)
  • half life is important as signal concentration cannot change quickly if the signal is not broken down quickly.
  • e.g. if phosphorylation is an important part of signaling then there must also be rapid dephosphorylation to keep background signal level low.
  • speed of response of a cell also depends on turnover of internal chemical (p837-838).