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PubMed1980

[Axonal transport from the nerve ending to the nerve cell body: a pathway for trophic signals and neurotoxins].

Nerve cells with their very long axons and dendrites have an effective system of anterograde and retrograde transport. In the retrograde direction there is, in addition to endogeneous cell constituents, a substantial transport of exogenous material like e.g. trophic factors like NGF. We have found that molecules which bind with high affinity to receptors in the nerve teminal surface membranes (e.g. NGF, tetanus and cholera toxin, lectins) are selectively internalized and transported retrogrdely to the cell body. Although most of them are incorporated into lysosomes in the cell body, they can nevertheless exert specific signal functions in the cell (NGF). Tetanus toxin, however, is released by the dendrites and transferred trans-synaptically to higher order neurons. We suggest that this retrograde and trans-synaptic transport represents an important pathway for "trophic" signal molekules, which convey information from the target cells to the innervating neurons. The same pathways can be used by neurotoxins *tetanus toxin) and neurotrophic viruses for entering the nervous system.

Animals↗
PubMed2006

Kinesin-2 differentially regulates the anterograde axonal transports of acetylcholinesterase and choline acetyltransferase in Drosophila.

Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) are involved in acetylcholine synthesis and degradation at pre- and postsynaptic compartments, respectively. Here we show that their anterograde transport in Drosophila larval ganglion is microtubule-dependent and occurs in two different time profiles. AChE transport is constitutive while that of ChAT occurs in a brief pulse during third instar larva stage. Mutations in the kinesin-2 motor subunit Klp64D and separate siRNA-mediated knock-outs of all the three kinesin-2 subunits disrupt the ChAT and AChE transports, and these antigens accumulate in discrete nonoverlapping punctae in neuronal cell bodies and axons. Quantification analysis further showed that mutations in Klp64D could independently affect the anterograde transport of AChE even before that of ChAT. Finally, ChAT and AChE were coimmunoprecipitated with the kinesin-2 subunits but not with each other. Altogether, these suggest that kinesin-2 independently transports AChE and ChAT within the same axon. It also implies that cargo availability could regulate the rate and frequency of transports by kinesin motors.

Acetylcholine↗
PubMed1987

A quantitative study of anterograde and retrograde axonal transport of exogenous proteins in olfactory nerve C-fibers.

The pike olfactory nerve which consists of a homogeneous population of C-fibers of 0.25 micron diameter or less was used to study quantitatively both anterograde and retrograde axoplasmic transport of wheat germ agglutinin and horseradish peroxidase. It was found that even in these extremely thin axons anterograde and retrograde transport takes place. Activity distribution profiles (transport profiles) for retrograde transport were established and found to be similar to the typical profiles of anterograde transport as they consisted of a small rapidly moving peak and a saddle region followed by the bulk of the material which moved more slowly. Horseradish peroxidase activity profiles were obtained both after injection into the synaptic region and after injection into the perikaryal region. From these transport profiles a maximal velocity of 25 mm/d (19 degrees C) for the leading peak and of about 7 mm/d for the slower component could be determined. There is no significant difference between the velocities for anterograde and retrograde transport. In the case of wheat germ agglutinin, only injection into the synaptic region resulted in typical transport profiles (retrograde transport) with a peak and saddle region. The maximum velocities of retrograde transport were about the same as for horseradish peroxidase [26 mm/d and 7 mm/d (19 degrees C)]. The electron microscopic analysis of horseradish peroxidase revealed that after injection into the olfactory bulb it was taken up into the neurons where it was found mainly in multivesicular bodies (0.5 micron diameter). In longitudinal sections of the nerve similar but slightly more elongated organelles (diameter 0.25 micron, length 0.4 micron) were found in those segments in which the slowly moving bulk of the peroxidase activity was located. The number of these organelles decreased with distance from the site of injection. The horseradish peroxidase transported within the leading peak could not be assigned to specific structures although several electron microscopic-histochemical methods were applied. It was concluded that anterograde and retrograde transport occur simultaneously in these axons, and that, therefore, even the large organelles, each of which almost fills the axon, must be able to pass each other. This would necessitate that the axons are able to transiently enlarge their diameter considerably.

Animals↗
PubMed2003

Neurofilament heavy chain side arm phosphorylation regulates axonal transport of neurofilaments.

Neurofilaments possess side arms that comprise the carboxy-terminal domains of neurofilament middle and heavy chains (NFM and NFH); that of NFH is heavily phosphorylated in axons. Here, we demonstrate that phosphorylation of NFH side arms is a mechanism for regulating transport of neurofilaments through axons. Mutants in which known NFH phosphorylation sites were mutated to preclude phosphorylation or mimic permanent phosphorylation display altered rates of transport in a bulk transport assay. Similarly, application of roscovitine, an inhibitor of the NFH side arm kinase Cdk5/p35, accelerates neurofilament transport. Analyses of neurofilament movement in transfected living neurons demonstrated that a mutant mimicking permanent phosphorylation spent a higher proportion of time pausing than one that could not be phosphorylated. Thus, phosphorylation of NFH slows neurofilament transport, and this is due to increased pausing in neurofilament movement.

Amino Acid Sequence↗
PubMed1983

Brainstem projections to the facial nucleus of the opossum. A study using axonal transport techniques.

The horseradish peroxidase and autoradiographic techniques have been used to determine the origin and intranuclear termination of brainstem axons projecting to the facial nucleus of the opossum and to define networks which could be utilized in some oral-facial behaviors. Two regions of the midbrain have dense projections to the facial nucleus. One region is the ventral periaqueductal gray and adjacent interstitial nucleus of the medial longitudinal fasciculus which project bilaterally to those areas of the facial nucleus supplying auricular and cervical musculature. A second is the paralemniscal zone of the caudolateral midbrain which innervates the same areas of the contralateral facial nucleus. The red nucleus and/or the adjacent tegmentum send a less dense projection to those regions of the contralateral facial nucleus which innervate buccolabial and zygomatic muscles. The dorsolateral pons (the parabrachial complex, the nucleus locus coeruleus, pars alpha, and the nucleus sensorius n. trigemini, pars dorsalis) projects densely to those areas of the ipsilateral facial nucleus which innervate buccolabial and zygomatic musculature. In contrast, the nucleus reticularis pontis, pars ventralis, projects bilaterally to parts of the facial nucleus supplying auricular and cervical muscles. There was evidence of some rostral to caudal organization in the latter projection. Neurons in medial parts of the lateral reticular formation project bilaterally to the facial nucleus. Those within the nucleus reticularis parvocellularis and the rostral nucleus reticularis medullae oblongatae ventralis innervate areas supplying buccolabial and zygomatic muscles. Neurons in the nucleus reticularis medullae oblongatae ventralis located caudal to the obex favor regions of the facial nuclei which supply auricular and cervical muscles. Neurons in the nucleus reticularis medullae oblongatae dorsalis and lamina V of the medullary and spinal dorsal horns project ipsilaterally to the facial nucleus in a manner suggesting that information from specific cutaneous areas reaches neurons supplying the muscles deep to them. The brainstem-facial connections are discussed in relation to the functionally diverse roles served by the facial nucleus in oral-facial behavior.

Animals↗
PubMed2005

Stochastic simulation of neurofilament transport in axons: the "stop-and-go" hypothesis.

According to the "stop-and-go" hypothesis of slow axonal transport, cytoskeletal and cytosolic proteins are transported along axons at fast rates but the average velocity is slow because the movements are infrequent and bidirectional. To test whether this hypothesis can explain the kinetics of slow axonal transport in vivo, we have developed a stochastic model of neurofilament transport in axons. We propose that neurofilaments move in both anterograde and retrograde directions along cytoskeletal tracks, alternating between short bouts of rapid movement and short "on-track" pauses, and that they can also temporarily disengage from these tracks, resulting in more prolonged "off-track" pauses. We derive the kinetic parameters of the model from a detailed analysis of the moving and pausing behavior of single neurofilaments in axons of cultured neurons. We show that the model can match the shape, velocity, and spreading of the neurofilament transport waves obtained by radioisotopic pulse labeling in vivo. The model predicts that axonal neurofilaments spend approximately 8% of their time on track and approximately 97% of their time pausing during their journey along the axon.

Algorithms↗