How short and dense are axonal microtubules? Approaches for analyzing microtubule organization and dynamics

Axons are cable-like extensions of neurons that conduct nerve impulses and relay information to subsequent cells at synapses. Their length varies dramatically, from micrometers in small invertebrates to over a meter in some neurons of large vertebrates. The cytoskeleton is the most important internal structure that determines neuronal morphology. Microtubules, in particular, play a crucial role in maintaining axonal structure, transport, and function. The classical view of axonal microtubules as long, continuous, and stable polymers extending over vast distances is being challenged by evidence suggesting that the axonal microtubule network is composed of overlapping microtubule fragments of varying lengths and is considerably dynamic. In this article, we describe how the unique organization of the axonal microtubule network has been elucidated in parallel with the development of novel microscopy techniques that provide high-resolution structural data and information on microtubule dynamics in neurons. We discuss how this unique microtubule architecture confers structural stability and adaptability to axons and hypothesize that the length distribution of microtubules reveals whether microtubule organization is more dynamic and adaptable or functions primarily as a stabilizing backbone for the axon shaft. Finally, we discuss potential future perspectives, both in terms of technological advances and open questions regarding the role of alterations in axonal microtubule arrangement in the aging process and neurodegenerative diseases.