Abstract
The hallmarks of neurons are their slender axons which represent the longest cellular processes of animals and which act as the cables that electrically wire the brain, and the brain to the body. Axons extend along reproducible paths during development and regeneration, and they have to be maintained for the lifetime of an organism. Both axon extension and maintenance essentially depend on the microtubule (MT) cytoskeleton. For this, MTs organize into parallel bundles that are established through extension at the leading axon tips within growth cones, and these bundles then form the architectural backbones, as well as the highways for axonal transport essential for supply and intracellular communication. Axon transport over these enormous distances takes days or even weeks and is a substantial logistical challenge. It is performed by kinesins and dynein/dynactin, which are molecular motors that form close functional links to the MTs they walk along. The intricate machinery which regulates MT dynamics, axonal transport and the motors is essential for nervous system development and function, and its investigation has huge potential to bring urgently required progress in understanding the causes of many developmental and degenerative brain disorders. During the last years new explanations for the highly specific properties of axonal MTs and for their close functional links to motor proteins have emerged, and it has become increasingly clear that motors play active roles also in regulating axonal MT networks. Here, I will provide an overview of these new developments.
Highlights
Axons are the longest cellular processes produced by animals
An appealing model has been put forward suggesting that dynein/dynactin might remove wrongly oriented MTs through retrograde MT transport, instead of chopping them up, like Hydra's head that would sprout new ones in their place, by using generated MT fragments as nucleation sites [56]. These few examples may only be the tip of the iceberg and more MTregulating roles of molecular motors contributing to the cellular processes underlying axon maintenance might well be discovered, but not necessarily roles and mechanisms that might be expected at this stage
There is an intricate relationship between MTs, the mechanisms that drive their nucleation,polymerization, cross-linkage and modification, and the motors that use them for transport and influence them in their regulation
Summary
Axons are masterpieces of biology and their study has fascinated neurobiologists since they were first described in the second half of the 19th century [1]. An appealing model has been put forward suggesting that dynein/dynactin might remove wrongly oriented MTs through retrograde MT transport, instead of chopping them up, like Hydra's head that would sprout new ones in their place, by using generated MT fragments as nucleation sites [56] These few examples may only be the tip of the iceberg and more MTregulating roles of molecular motors contributing to the cellular processes underlying axon maintenance might well be discovered, but not necessarily roles and mechanisms that might be expected at this stage
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