Axonal Transport

Impulse conduction is not the sole function of the axon. Macromolecules essential to structure flow from the soma down the axon. Other substances, e.g., tired axon terminal membrane requiring degradation and recycling, move up. Rates of axonal transport of these commodities vary strikingly; some, including newly synthesized protein for neuronal repair, move slowly, at 0.2-5 mm/day, whereas others related to transmitter synthesis travel 100-400 mm/day. Two modes of axonal transport are known: fast, bidirectional (ante-rograde and retrograde) and slow, unidirectional (anterograde only).

Mechanisms of axonal transport have been studied intensively. Microtubules play a critical role in fast transport. Axonal microtubules are polarized: their ''plus'' ends face the axon terminal and their ''minus'' ends the cell body. Microtubules constantly turn over; tubulin dimers are added at the plus ends and depolymerized at the minus ends. Neuronal products are shipped down the axon as small vesicles. Kinesin, a microtubule-associated protein, is the motor responsible for this transport. One end of a kinesin molecule attaches to a vesicle while a binding site on the other end interacts in a cyclical manner with the wall of a microtubule, resulting in movement of the vesicle toward the plus end at about 3 mm/s.

In fast anterograde axonal transport, outbound materials are membrane-bound organelles from the rER and Golgi complex, synaptic vesicle precursor membranes, large dense-core vesicles, parts of the smooth ER, and mitochondria. This transport travels along microtubules, stationary raillines and fast tracks along which shipments are moved by molecular motors (kinesin and related proteins) at high speed (100-400 mm/day). It meets the critical, unceasing needs of neurotransmission.

In fast retrograde axonal transport, the incoming materials are endosomes (micropinocytotic vesicles) from nerve terminals, mitochondria, and ER elements returning to the soma from axon terminals. This transport travels on microtubules as in the preceding paragraph, but at half to two-thirds the speed. The motor is a microtubule-associated ATPase similar to dynein in cilia and flagella. It provides for degradation and further recycling in cell body lysosomes of worn-out membrane components, which may have already been recycled a few times in the terminals. It also implies processing and repackaging events there, much as one must evaluate and rewrap damaged goods prior to returning to the sender.

Slow anterograde-only axonal transport is for cytosol proteins and cytoskeletal elements. It has two rates: slow and slower. Slow (rate b: 2.5-5 mm/day) conveys hundreds of polypeptides from cytoskeletal proteins (like actin) to soluble metabolic (e.g., glycolytic) enzymes. Slower (rate a: 0.2-2.5mm/day) is mainly (75% of the total moved) neurofibrillary protein: neurofilament and microtubule subunits. Motors are uncertain; dynein may be one. Neurofilaments seem unable to move on their own but may hitchhike on microtubules, which can extend themselves (see previous discussion). Slow axonal transport maintains the structural and functional integrity of remote regions of the neuron: perhaps 10,000 times the diameter of the cell body away.

The mechanisms of axonal transport have been explained to a degree that is a triumph for molecular neurobiology. Study of the perpetual movement of materials along the axon clarifies other aspects of neuronal activity, especially the regeneration of PNS axons, which takes place at about 1-3 mm/day, and the daily shipment and delivery of neuroactive substances and their precursors.

Axonal transport is vital to the life of the neuron and its communicative and neurotrophic functions. It permits rapid replacement of catabolized protein in the axon and its terminals. Most constituents of such a protein cannot be synthesized in the axoplasm devoid of rER. It permits the transport of enzymes synthesized in the soma down to the axon terminals; such enzymes are necessary for transmitter synthesis there. It permits the movement of macromolecules and other dynamic cellular components within the soma itself and out into the dendrites, which have modest protein-synthetic capability.

In retrospect, ''axonal transport'' exemplifies tunnel vision. ''Intraneuronal transport'' might have been a better way to designate mechanisms of moving materials within neurons had we known then what we know now. It permits feedback from the periphery (axon terminals and dendrites) and regulation of the metabolic activity of the parent cell body: adjusting rates of protein and enzyme synthesis or reprocessing worn-out membrane components in accord with peripheral use and demand.

Experimental benefits and some risks accrue from axonal transport. A powerful neuroanatomical method for tracing axons back to their cells of origin rests upon the uptake by axon terminals of tiny enzyme particles (the glycoprotein horseradish peroxidase) and retrograde axonal transport to the somata. There, these markers can be demonstrated histochemically as a colored, insoluble polymer. Unfortunately, retrograde transport also may convey pathogens (tetanus bacterial toxin, herpes simplex, and rabies viruses) directly to nerve cell bodies, once the microorganisms are endocytosed at nerve endings. A technique exploiting anterograde axonal transport is the autoradiographic method. Radioactively labeled amino acid is injected near a nerve cell body, taken up by the cell, incorporated into newly synthesized protein, and then transported down the axon to its terminals. There, the radioactivity can be detected by autoradiography (a process similar to photography).

Breaking Bulimia

Breaking Bulimia

We have all been there: turning to the refrigerator if feeling lonely or bored or indulging in seconds or thirds if strained. But if you suffer from bulimia, the from time to time urge to overeat is more like an obsession.

Get My Free Ebook


Post a comment