Tuesday, May 26, 2009

Stirring Up the Cytoplasm


I wrote a while back in the fourth part of my series on cellular intelligence about localized calculations and the role of diffusion in both localizing them and slowing down any calculation that must cross significant distances. As several of the refereneces in that post demonstrated,4, 5, 6, 7, 8, 9 signal propagation over longer distances than is possible with diffusion require some sort of active movement.

Two recent papers I hadn't previously discovered offer information in this regard.2, 3

Brangwynne, C., Koenderink, G., MacKintosh, F., & Weitz, D. (2008). Cytoplasmic diffusion: molecular motors mix it up The Journal of Cell Biology, 183 (4), 583-587 DOI: 10.1083/jcb.200806149

Kulic, I., Brown, A., Kim, H., Kural, C., Blehm, B., Selvin, P., Nelson, P., & Gelfand, V. (2008). The role of microtubule movement in bidirectional organelle transport Proceedings of the National Academy of Sciences, 105 (29), 10011-10016 DOI: 10.1073/pnas.0800031105

What these papers demonstrate is that the cytoplasm is a very active substance, constantly being stirred by the movements of microtubules as they squirm like slinkies under the influence of various molecular motors. The resulting movement is random, in some ways like Brownian motion, but covers a much larger scale.

This has very important implications for cellular calculations. There are many ways in which specific processes could be localized when necessary, but there probably isn't any real need for a dedicated transport system for most signals; only the most time-critical would need such things. Most reactions within the cell could be kept synchronized by this pseudo-Brownian motion.

This would certainly be true for all the known developmental signals, few if any of which resolve in time-frames less than 10's of minutes, while the velocities involved in this movement are measured in microns/second, plenty of time for cell-wide signals to be propagated.

There are special aspects when it comes to neurons. In the dendrites, the very recent history of action potentials can influence the concentration of a variety of enzymes and other signaling molecules that can, in turn, influence the activity of ion channels in the membranes of the dendrites nearby.

Given that there are bundles of microtubules running down most dendrites, the demonstration that these are intimately associated with rapid, random movement, both longitudinal and lateral, means that we can expect a greater potential intelligence in the membrane of the dendrite as it responds to electrical waves from synapses more distant from the soma.

These papers represent important information in our efforts to understand how the cell "thinks", especially in the case of neurons.

Links: Not every link here is called out in the text. Use the back key if you got here via a footnote.

1. Role of the cytoskeleton in signaling networks

2. Cytoplasmic diffusion: molecular motors mix it up

3. The role of microtubule movement in bidirectional organelle transport

4. Diffusion control of protein phosphorylation in signal transduction pathways

5. Signaling cascades as cellular devices for spatial computations

6. Enzyme Localization Can Drastically Affect Signal Amplification in Signal Transduction Pathways

7. Four-dimensional organization of protein kinase signaling cascades: the roles of diffusion, endocytosis and molecular motors

8. Modeling the signaling endosome hypothesis: Why a drive to the nucleus is better than a (random) walk

9. Why the Phosphotransferase System of Escherichia coli Escapes Diffusion Limitation

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