To Nucleate or Not, That is the Question in Neurons

Microtubules are the structural center of neurons, stretching in overlapping arrays from the cell body to the far reaches of axons and dendrites. They also act as the tracks for long-range transport mediated by dynein and kinesin motors. Transcription and most translation take place in the cell body, and newly made cargoes must be shipped from this site of synthesis to sites of function in axons and dendrites. This constant demand for transport means that the microtubule array must be present without gaps throughout the cell over the lifetime of the animal. This task is made slightly easier in many animals by the relatively long, stable microtubules present in neurons. However, even stable neuronal microtubules have ends that are dynamic, and individual microtubules typically last on the order of hours, while the neurons around them last a lifetime. "Birth" of new microtubules is therefore required to maintain the neuronal microtubule array. In this review we discuss the nucleation of new microtubules in axons and dendrites, including how and where they are nucleated. In addition, it is becoming clear that neuronal microtubule nucleation is highly regulated, with unexpected machinery impinging on the decision of whether nucleation sites are active or inactive through space and time.