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ULTIMATE COMPUTING - Quantum Consciousness Studies

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92 Cytoskeleton/Cytocomputer<br />

Disassembly or separation of tubulin dimer subunits from MT is induced<br />

when terminal dimers bind GDP. When GTP is hydrolyzed, a phosphate group is<br />

lost and guanosine triphosphate (GTP) becomes guanosine diphosphate (GDP).<br />

GTP bound dimers at open ends of MT (GTP “caps”) are stable: they stay<br />

assembled. However, when open ends of MT contain subunits binding GDP, they<br />

tend to release and shorten the MT cylinder. MT whose distal ends have exposed<br />

GDP tubulin, and are not anchored by structures like MTOC, shrink and<br />

depolymerize. Generally, free MT polymers (those not anchored by MTOC) are<br />

“chimeric” with stretches of unhydrolyzed GTP at the ends (GTP caps) and GDP<br />

in the interior. Growing polymers have “protective” GTP subunit caps at their<br />

end; shrinking polymers lose their GTP caps and expose GDP subunits at the end,<br />

causing disassembly.<br />

Microtubules thus appear to exist in two populations: the majority growing at<br />

an appreciable rate and the minority shrinking very rapidly and providing new<br />

subunits for growth. This concept has been called “dynamic instability” with the<br />

rapid shrinkage of MT referred to as “microtubule catastrophes” (Kirschner and<br />

Mitchison, 1986). The faster the growth rate, the larger the GTP cap and the lower<br />

the probability of the cap disappearing and the microtubule depolymerizing.<br />

When the cap disappears and GDP subunits are exposed, the polymer enters a<br />

rapid depolymerizing (“catastrophic”) phase. MT contain thirteen parallel<br />

protofilaments and it is unclear how many exposed GTP or GDP containing<br />

subunits at MT terminals are required for stability or instability. An essential<br />

factor is the rate of GTP hydrolysis which results in GDP tubulin and induces<br />

disassembly. The utilization of GTP hydrolysis energy by MT and the<br />

cytoskeleton is a significant portion of biological energy consumption, yet<br />

remains unappreciated. Theories of protein conformational state regulation such<br />

as solitons and coherent excitations which could account for the useful<br />

consumption of hydrolysis energy will be described in Chapter 6. Solitons,<br />

coherent lattice vibrations, and cooperative resonance present possibilities for<br />

collective, and possibly intelligent effects within cells.<br />

Japanese investigators Horio and Hotani (1986) have directly observed<br />

growing and shrinking MT using dark field microscopic video. They observed<br />

that both ends of a microtubule can exist in either the growing or the shortening<br />

phase and alternate quite frequently between the two phases in an apparently<br />

random manner. Further, growing and shortening ends can coexist on a single<br />

microtubule: treadmilling. One end may continue to grow simultaneously with<br />

shortening at the other end. The two ends of any given microtubule have<br />

remarkably different characteristics. One “active” end (presumably the beta, plus<br />

end) grows faster, alternates in phase between growing and shrinking more<br />

frequently, and fluctuates in length to a greater extent than the inactive end.<br />

Microtubule associated proteins (“MAPs”) suppress the phase conversion and<br />

stabilize microtubules in the growing phase.<br />

There are many apparent mechanisms for stabilizing polymerized<br />

microtubules: they may be capped or bound to various structures. Binding at the<br />

proximal end to MTOCs stabilizes MT and prevents their depolymerizing at the<br />

opposite end. MT need to be stabilized at merely one end to predominate within<br />

cells because, even if they depolymerize, another will reform in the same place<br />

and orientation (DeBrabander, 1985). Thus MTOC provide cells with a means of<br />

selective retention of a subclass of specifically oriented MT.<br />

MTOC oriented in a specific direction can determine cell polarity, including<br />

extension of cells in embryological growth, formation of probing appendages<br />

called filopodia in locomotory cells and growth of nerve processes. Signals at the<br />

cell periphery apparently cause an asymmetry of the microtubule cytoskeleton

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