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Biomedical subjects

M J Katz

Publications and source records attributed to M J Katz.

At least 19 recordsLinked to original sources
PubMed1993

The maximum rate of neurofilament transport in axons: a view of molecular transport mechanisms continuously engaged.

Neurofilaments (NFs) were radiolabeled in the optic systems of mice. The leading edge of the radiolabeled NF waveform was distinguished near the injection site (the eye) both by liquid scintillation spectroscopy and visually from fluorographs. The fastest NFs were found to be translocated at rates of between 72 and 144 mm/day. It appears that the continuous (maximal) operation of the slow axonal transport machinery can move polymers intra-axonally at rates one hundred times greater than those previously reported.

Animals↗
PubMed1993

Neurofilaments assume a less random architecture at nodes and in other regions of axonal compression.

Neurofilament distributions were mathematically characterized in four chicken somatic motor axons at each of four histologically distinct regions: compact myelinated regions, compact myelinated regions associated with Schwann cell nuclei, Schmidt-Lanterman clefts, and nodes of Ranvier. Compact myelinated regions had the largest cross-sectional areas, the lowest neurofilament densities, and the most random neurofilament organizations--nodes of Ranvier had the smallest cross-sectional areas, the highest neurofilament densities, and the most ordered architectures. In these myelinated axons, the closest natural neurofilament spacing was 25 nm. Mathematical analyses of serial sections suggested that neurofilament interactions are sufficiently weak and transient to permit a full range of variation from random to ordered cytoskeletal architectures as the neurofilaments move longitudinally through the few micron span of the paranodal-nodal region of a single axon.

Animals↗
PubMed1992

Slow axonal transport mechanisms move neurofilaments relentlessly in mouse optic axons.

Pulse-labeling studies of slow axonal transport in many kinds of axons (spinal motor, sensory ganglion, oculomotor, hypoglossal, and olfactory) have led to the inference that axonal transport mechanisms move neurofilaments (NFs) unidirectionally as a single continuous kinetic population with a diversity of individual transport rates. One study in mouse optic axons (Nixon, R. A., and K. B. Logvinenko. 1986. J. Cell Biol. 102:647-659) has given rise to the different suggestion that a significant and distinct population of NFs may be entirely stationary within axons. In mouse optic axons, there are relatively few NFs and the NF proteins are more lightly labeled than other slowly transported slow component b (SCb) proteins (which, however, move faster than the NFs); thus, in mouse optic axons, the radiolabel of some of these faster-moving SCb proteins may confuse NF protein analyses that use one dimensional (1-D) SDS-PAGE, which separates proteins by size only. To test this possibility, we used a 2-mm "window" (at 3-5 mm from the posterior of the eye) to compare NF kinetics obtained by 1-D SDS-PAGE and by the higher resolution two-dimensional (2-D) isoelectric focusing/SDS-PAGE, which separates proteins both by their net charge and by their size. We found that 1-D SDS-PAGE is insufficient for definitive NF kinetics in the mouse optic system. By contrast, 2-D SDS-PAGE provides essentially pure NF kinetics, and these indicate that in the NF-poor mouse optic axons, most NFs advance as they do in other, NF-rich axons. In mice, greater than 97% of the radiolabeled NFs were distributed in a unimodal wave that moved at a continuum of rates, between 3.0 and 0.3 mm/d, and less than 0.1% of the NF population traveled at the very slowest rates of less than 0.005 mm/d. These results are inconsistent with the proposal (Nixon and Logvinenko, 1986) that 32% of the transported NFs remain within optic axons in an entirely stationary state. As has been found in other axons, the axonal transport system of mouse optic axons moves NFs and other cytoskeletal elements relentlessly from the cell body to the axon tip.

Animals↗
PubMed1991

Microtubules have special physical associations with smooth endoplasmic reticula and mitochondria in axons.

Ultrastructural morphometry was used to document the non-random spatial distributions of organelles within the compact myelinated region of avian oculomotor axons. These regions contain large numbers of loosely packed neurofilaments (NFs) (241/microns 2) and only a relatively small number of microtubules (MTs) (4/microns 2), mitochondria (0.6/microns 2), and smooth endoplasmic reticulum (SER) (1.6/microns 2). Random co-occurrences between the relatively sparsely distributed MTs, mitochondria, and SER are probably infrequent in these axons. The actual co-occurrences of MTs, mitochondria, and SER with MTs were counted and compared to the co-occurrences expected in a random Poisson distribution. At long distances (200 nm), the co-occurrences were random. At shorter distances (40 nm and less), MTs were still randomly associated with other MTs. However, at these shorter distances, the spatial associations of mitochondria with MTs and of SER with MTs were not random; such preferential stable associations may be produced by specific MT associated cross-bridging proteins. In axons, MTs tend to be clustered together, giving the appearance of MT bundles. We propose that the MT-MT bundling is an indirect result of MT concentration along the continuous intra-axonal SER network, to which the MTs are apparently tied directly by dynamic molecular cross-bridges.

Animals↗
PubMed1990

Internal axonal cytoarchitecture is shaped locally by external compressive forces.

The cross-sectional architecture of the axon and the area of its surrounding Schwann cell were quantified at selected histological regions along the length of avian myelinated axons. The number of neurofilaments (NFs), the density of NFs, axoplasmic area, and Schwann cell cross-sectional area were measured. These parameters were examined at Schmidt-Lanterman (S-L) clefts, at paranodal-nodal regions, and at regions of compact myelin Schwann cell nuclei. The results were then compared with the same parameters in adjacent compact myelinated regions of the same axons. At S-L clefts, paranodal-nodal regions, and Schwann cell nuclei, the axonal areas were smaller and the NF densities were higher than at compact myelinated regions. From other studies, it has been suggested that NF organization is responsive to local compressive forces--NF packing density tends to increase with increasing compression of the axon. We found that the NF packing densities were relatively small and the axon diameters were relatively large in the compact myelinated regions; this result suggests that in these axonal regions external constraints on axonal architecture are minimal. The higher NF packing densities and smaller axon diameters in the other histological regions suggest that external compressive effects on the axon increase in the following order: simple compact myelin less than Schwann cell nucleus less than S-L cleft less than paranodal-nodal region. Ultrastructural comparisons of these 4 histological regions show that the Schwann cell cross-sectional areas differ reproducibly, and this is consistent with the idea that variations in the organization of extra-axonal elements that envelop the axon produce different amounts of physical constraint on the axon and that this can affect the amount of external pressure on the internal architecture of the axon.

Animals↗
PubMed1990

Cytomatrix protein residence times differ significantly between the tract and the terminal segments of optic axons.

The window method of radiolabeled protein analysis was used to study the transport kinetics of axonally transported cytomatrix proteins as they move through segments of mouse optic axons. Three slow component b (SCb) proteins--actin, a 30 kDa protein, and clathrin--were radiolabeled in the eye and were followed for up to 119 days by quantitative one-dimensional gel electrophoresis. These proteins appeared first in the optic nerve, next in the tract, and last in the superior colliculus. All of the radiolabeled proteins had passed through the optic axons and had been effectively removed from the terminals by 119 days. Two different axonal segments ('windows') were examined in detail: a segment of the axon shaft region in the optic tract, and a segment of axon terminal region in the midbrain superior colliculus. The median transit times of the 3 proteins were 53-100% longer in the colliculus than in the tract, and the pulse transients (the total area under the transport curve in each window) were 180-350% larger in the colliculus than in the tract. These results indicate that at least certain cytomatrix and cytoskeletal proteins have longer residence times in the terminal regions than in the axon proper.

Actins↗
PubMed1989

Slow component B protein kinetics in optic nerve and tract windows.

The transport kinetics of 3 radiolabeled slow component b (SCb) proteins (a 30 kDa protein, clathrin, and actin) were examined in the axons of mouse retinal ganglion cells. To view the transit of these proteins through the entire optic pathway between the eye and the target cells, we used two different windows: (1) a 2 mm segment from the optic nerve located 3-5 mm from the eye, and (2) a 2 mm segment from the optic tract located past the chiasm 6-8 mm from the eye. The radiolabeled proteins from these windows were separated by 1- and 2-dimensional SDS-PAGE, and the individual radiolabeled bands were quantified. Radiolabeled proteins entered and cleared the optic axons between 1 and 119 days post-labeling. All these proteins had broader transport waves in the more distal optic tract window than in the more proximal optic nerve window. The spreading of transport waves as they advance along the axon appears to be produced by a playing out of the natural heterogeneity of axonal transport rates within each population of labeled proteins. Our results confirm the proposals that clathrin and the 30 kDa protein are transported principally with SCb and that actin is transported both with SCb and with SCa. Although these proteins can be generally classified with SCb, their detailed kinetics differed (for example, their median transit times differed) and, in summary, their characteristic rates of movement can be ordered as: clathrin greater than 30 kDa protein greater than actin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Experimental increase of neurofilament transport rate: decreases in neurofilament number and in axon diameter.

In 2,5-hexanedione (2,5-HD)-induced axonal neuropathy, the rate of neurofilament (NF) transport increases in optic axons. To test the prediction that increases in the rate of polymer transport in any one locality of the axon lead directly to a decrease in the number of NF in that locality, NF and microtubules (MT) were quantitatively analyzed in axonal cross sections. In 2,5-HD axons the number of NF was 38% of that in control axons while the number of MT was not significantly changed; it appears that the drug treatment decreases NF number in the proximal axon regions, most directly through an increase in rate of NF transport. In those regions, the cross-sectional areas of the 2,5-HD-treated axons were 45% smaller than those of control axons; although the axons had shrunk in diameter, they retained their normal cylindrical shapes as measured by the index of circularity. Reduced internal expansive forces in the axon, working in conjunction with the normal external compressive forces, appear to reduce the radius of the axon. Quantitative analyses demonstrated that the average and the maximum lateral spacings between NF-NF, NF-MT, and MT-MT were all 30% larger in 2,5-HD-treated axons than in control axons. This suggests that polymers are relatively free to move laterally away from one another and to fill the available space within the axon. These observations are not consistent with models wherein 2,5-HD acts to crosslink the NF into an immobile network that can no longer advance within the axon. Instead, it appears more likely that 2,5-HD acts selectively on the interaction between some NF and the slow transport mechanism to increase the rate of NF transport.

Animals↗
PubMed1988

Axonal shortening and the mechanisms of axonal motility.

Axons in tissue culture retract and shorten if their tips are detached from the substrate. The shortening reaction of the axon involves contractile forces that also arise during normal axonal motility, elongation, and retraction. We studied shortening in axonal segments isolated from their parent axons by transecting the axon between the growth cone and the most distal point of adhesion to the substrate. Within 15-20 minutes after transection, an isolated axonal segment shortened and pulled its tail end toward the growth cone. During the shortening process, long sinusoidal bends arose along the axon. The identical shortening reaction occurs without transection, when the axon tip is detached from the substrate. Pharmacological studies with inhibitors of glycolysis indicate that the shortening mechanisms utilize metabolic energy, presumably ATP. The rate of sinusoidal shortening is similar to both the rate of polymer translocation in the axon by slow axonal transport and the rate of normal axonal elongation. Taxol inhibits the shortening reaction with a similar dose dependence to its inhibition of axonal growth. Together, all these observations suggest that the same basic intracellular motility mechanisms are involved in normal axonal growth, in slow axonal transport, and in the shortening reaction: the intracellular dynamic system that utilizes ATP to generate longitudinal movements of polymers within the axon may be the same mechanism underlying both the retraction and the elongation of the axon.

Alkaloids↗
PubMed1988

Neurofilaments are spaced randomly in the radial dimension of axons.

The organization of the cytoskeleton is compared in the large myelinated parasympathetic and somatic motor axons of the avian oculomotor system. Electron microscopic studies demonstrate that neurofilaments are the chief structural elements in these axons, and quantitative analyses of the distribution of neurofilaments in axonal cross-sections found that the average neurofilament packing density is 25% greater in the parasympathetic axons than in the somatic motor axons. In both types of axon the distributions of neurofilaments matched a randomly generated (Poisson) distribution. In axoplasm, a Poisson distribution could arise if the neurofilaments were distributed in the cross-sectional plane by stochastic forces operating randomly and without significant neurofilament-neurofilament interactions. Thus, in these axons, the neurofilaments behave as if they are inert 'molecules' in a dilute solution-subject to non-specific stochastic forces that tend to distribute them at random. We propose that neurofilaments normally are relatively free to move apart from each other and to fill the available space within the axon.

Animals↗
PubMed1988

Fractals and the analysis of waveforms.

Waveforms are planar curves--ordered collections of (x, y) point pairs--where the x values increase monotonically. One technique for numerically classifying waveforms assesses their fractal dimensionality, D. For waveforms: D = log(n)/(log(n) + log(d/L], with n = number of steps in the waveform (one less than the number of (x, y) point pairs), d = planar extent (diameter) of the waveform, and L = total length of the waveform. Under this formulation, fractal dimensions range from D = 1.0, for straight lines through approximately D = 1.15 for random-walk waveforms, to D approaching 1.5 for the most convoluted waveforms. The fractal characterization may be especially useful for analyzing and comparing complex waveforms such as electroencephalograms (EEGs).

Biological Evolution↗
PubMed1987

Preferred microtubules for vesicle transport in lobster axons.

The hypothesis that transported vesicles are preferentially associated with a subclass of microtubules has been tested in lobster axons. A cold block was used to collect moving vesicles in these axons; this treatment caused the vesicles to accumulate in files along some of the microtubules. Quantitative analysis of the number of vesicles associated with microtubule segments indicated that lobster axons have two distinct populations of microtubules--transport microtubules that are the preferred substrates for vesicle transport and architectural microtubules that contribute to axonal structure.

Animals↗
PubMed1986

Quantitative effects of NGF on the growth of embryonic frog axons.

Sparse, dissociated cultures of embryonic Xenopus CNS neurons were grown with and without NGF. Under both conditions the same number of neurons survived and extended neurites, and under both conditions the neurites moved at approximately the same overall rates and with the same degree of straightness. On the other hand, neurons in the NGF-supplemented cultures had more neurites and these neurites branched 64% more often. Detailed measurements showed that the axons elongated 44% faster in NGF and that this increase could be ascribed to a selective increase in the stepping rate of axonal elongation. These observations raise the possibility that NGF may selectively modulate the rate of movement of the core cytoskeleton of the axon.

Animals↗
PubMed1985

Axonal branch shapes.

To distinguish the relative roles of the intrinsic and the extrinsic determinants of axonal branching shapes, a number of key branch parameters were measured under a variety of conditions. Branch shapes of frog and of chick axons were analyzed in tissue culture, and these in vitro patterns were compared with in vivo branch patterns of axons in tadpole tail fins. The shape of a branch junction can be characterized by the sizes of its branch angles. In all cases, branch junctions had only two branches (3 branch angles), and the bifurcation angle between them was usually the smallest. The shape of the branch junction was constant in a wide variety of environments, but the exact branch angles, as well as the numbers of branches per axon and the numbers of axons per neuron, could be modulated by changes in the substrate adhesivity.

Animals↗
PubMed1985

Templeting and self-assembly.

Templeting and self-assembly represent the two extremes of the spectrum of determinate pattern-assembly processes. A templeted pattern can be defined as one that requires a prepattern or templet explicitly specifying the final topology of the pattern. Conversely, a self-assembling pattern can be defined as one for which the inherent constraints of the precursor elements alone are sufficient to specify the final pattern. Both concepts can be directly expressed in matrix notation, and a simple matrix measure, the templeting index, characterizes the relative amount of templeting or of self-assembly in any particular system. With this language, a fundamental principle of pattern-assembly becomes evident: in the determinate realm, some patterns can only be assembled using the same-sized templets--templets that are at least as large as the final pattern.

Mathematics↗