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Thought Provoker



Posts: 530
Joined: April 2007

(Permalink) Posted: Sep. 24 2007,22:05   

Hi Jam,

You ask...
 
Quote
Are you trying to claim that Penrose was distinguishing anything from flagellar, ciliary, or spindle microtubules, or was he just adding extra polysyllabic words to his tome?

IMO, it's just part of an attempt to obfuscate his sloppy equivocation between the cytoskeleton and the microtubule cytoskeleton.

It has been suggested that I am wasting my time here.  That may be true in your case, but on the chance that others are listening in I will continue.

You continue to make reference to Penrose.  Penrose is not the biologist, Dr. Hameroff is.  To avoid confusion, let me quote from a paper written by Dr. Hameroff and NOT the physicist Penrose...

III. The neural correlate of consciousness

a. Functional organization of the brain

Most brain activities are nonconscious; consciousness is a mere “tip of the iceberg” of neural functions. Many brain activities—e.g. brainstem-mediated autonomic functions—never enter consciousness. While consciousness is erased during general anesthesia, nonconscious brain EEG and evoked potentials continue, although reduced.[xiv]

...

Membrane-based neuronal input-output activities involve changes in synaptic plasticity, ion conductance, neurotransmitter vesicle transport/secretion and gap junction regulation—all controlled by the intra-neuronal networks of filamentous protein polymers known as the cytoskeleton. If simple input-output activities fully described neural function, then fine-grained details might not matter. But simple input-output activities—in which neurons function as switches—are only a guess, and most likely a poor imitation of the neuron’s actual activities and capabilities.

To gauge how single neuron functions may exceed simple input-output activities, consider the single cell organism paramecium. Such cells swim about gracefully, avoid obstacles and predators, find food and engage in sex with partner paramecia. They can also learn; if placed in capillary tubes they escape, and when placed back in the capillary tubes escape more quickly. As single cells with no synaptic connections, how do they do it? Pondering the seemingly intelligent activities of such single cell organisms, famed neuroscientist C.S. Sherrington (1957) conjectured: “of nerve there is no trace, but the cytoskeleton might serve”. If the cytoskeleton is the nervous system of protozoa, what might it do for neurons?

IV. The neuronal cytoskeleton

a. Microtubules and networks inside neurons

Shape, structure, growth and function of neurons are determined by their cytoskeleton, internal scaffoldings of filamentous protein polymers which include microtubules, actin and intermediate filaments. Rigid microtubules (MTs) interconnected by MT-associated proteins (MAPs) and immersed in actin form a self-supporting, dynamic tensegrity network which shapes all eukaryotic cells including highly asymmetrical neurons. The cytoskeleton also includes MT-based organelles called centrioles which organize mitosis, membrane-bound MT-based cilia, and proteins which link MTs with membranes. Disruption of intra-neuronal cytoskeletal structures impairs cognition, such as tangling of the tau MAP linking MTs in Alzheimer’s disease (Matsuyama and Jarvik, 1989, Iqbal and Grundke-Iqbal 2004).

Actin is the main component of dendritic spines and also exists throughout the rest of the neuronal interior in various forms depending on actin-binding proteins, calcium etc. When actin polymerizes into a dense meshwork, the cell interior converts from an aqueous solution (sol state) to a quasi-solid, gelatinous (gel) state. In the gel state, actin, MTs and other cytoskeletal structures form a negatively-charged matrix on which polar cell water molecules are bound and ordered (Pollack 2001). Glutamate binding to NMDA and AMPA receptors triggers gel states in actin spines (Fischer et al 2000).

Neuronal MTs self-assemble, and with cooperation of actin enable growth of axons and dendrites. Motor proteins transport materials along MTs to maintain and regulate synapses. The direction and guidance of motor proteins and synaptic components (e.g. from cell body through branching dendrites) depends on conformational states of MT subunits (Krebs et al 2004). Thus MTs are not merely passive tracks but appear to actively guide transport. Among neuronal cytoskeletal components, MTs are the most stable and appear best suited for information processing Wherever cellular organization and intelligence are required, MTs are present and involved.

MTs are cylindrical polymers 25 nanometers (nm = 10-9 meter) in diameter, comprised of 13 longitudinal protofilaments which are each chains of the protein tubulin (Figure 8). Each tubulin is a peanut-shaped dimer (8 nm by 4 nm by 5 nm) which consists of two slightly different monomers known as alpha and beta tubulin, (each 4 nm by 4 nm by 5 nm, weighing 55,000 daltons). Tubulin subunits within MTs are arranged in a hexagonal lattice which is slightly twisted, resulting in differing neighbor relationships among each subunit and its six nearest neighbors (Figure 9). Thus pathways along contiguous tubulins form helical pathways which repeat every 3, 5 and 8 rows (the Fibonacci series). Alpha tubulin monomers are more negatively charged than beta monomers, so each tubulin (and each MT as a whole) is a ferroelectric dipole with positive (beta monomer) and negative (alpha monomer) ends.[xxiii]

In non-neuronal cells and in neuronal axons, MTs are continuous and aligned radially like spokes of a wheel emanating from the cell center. MT negative (alpha) ends originate in the central cell hub (near the centrioles, or MT-organizing-center adjacent to the cell nucleus) and their positive (beta) ends extend outward to the cell perimeter. This is the case in axons, where the negative ends of continuous MTs originate in the axon hillock, and positive ends reach the pre-synaptic region.

However dendritic cytoskeleton is unique. Unlike axons and any other cells, MTs in dendrites are short, interrupted and mixed polarity. They form networks interconnected by MAPs (especially dendrite-specific MAP2) of roughly equal mixtures of polarity. There is no obvious reason why this is so—from a structural standpoint uninterrupted MTs would be preferable, as in axons. Networks of mixed polarity MTs connected may be optimal for information processing.  

Intra-dendritic MT-MAP networks are coupled to dendritic synaptic membrane and receptors (including dendritic spines) by mechanisms including calcium and sodium flux, actin and metabotropic inputs including second messenger signaling e.g. dephosphorylation of MAP2 (Halpain and Greengard 1990). Alterations in dendritic MT-MAP networks are correlated with locations, densities and sensitivities of receptors (e.g. Woolf et al 1999). Synaptic plasticity, learning and memory depend on dendritic MT-MAP networks.

Since Sherrington’s observation in 1957, the idea that the cytoskeleton—MTs in particular—may act as a cellular nervous system has occurred to many scientists. Vassilev et al (1985) reported that tubulin chains transmit signals between membranes, and Maniotis et al (1997a, 1997b) demonstrated that MTs convey information from membrane to nucleus. But MTs could be more than wires. The MT lattice is well designed to represent and process information, with the states of individual tubulins playing the role of bits in computers. Conformational states of proteins in general (e.g. ion channels opening/closing, receptor binding of neurotransmitter etc.) are the currency of real-time activities in living cells. Numerous factors influence a protein’s conformation at any one time, so individual protein conformation may be considered the essential input-output function in biology.


Here is a diagram and video showing microtubules appearing to actively orchestrate a cell dividing.

Here is a video that makes a mockery of thinking of microtubles as passive cytoskeletal components.

They one the DNA was just for structural support.  After all, how could something made up of only four bases be important?

  
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