To nucleate or not, that is the question in neurons

Abstract

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.

Keywords: Endosome; Kinetochore; Microtubule nucleation; Microtubule severing; Wnt signaling.

Figure 1.. Dendritic and axonal microtubule nucleation.

A. An overview of a neuron with key nucleation mechanisms indicated in axons and dendrites. Pink lines represent minus-end-out microtubules and green lines plus-end-out ones. Circles in dendrites show sites of endosomal nucleation and pink barbs indicate branched nucleation in axons. B. Summary of endosomal nucleation. A diagram of a dendrite branch point is shown containing an early endosome with Wnt signaling machinery to control microtubule nucleation. This diagram is based on nucleation in Drosophila sensory neuron dendrites. C. A region of an axon is shown containing a microtubule with the HAUS/augmin complex nucleating a new microtubules. This type of nucleation has been shown to occur in mammalian axons. The different pieces of the diagram linked by arrows indicate a time sequence. D. Developing dendrites in some invertebrate neurons have a hotspot of nucleation near the growth cone. This nucleates microtubules in both directions, but its position near the tip means that most of the dendrite is minus-end-out.

Figure 2.. Generation of growing minus ends after nucleation.

A speculative model of conversion of a capped minus end to a growing one is shown. Nucleation at dendrite branch points is shown as in Figure 1, and the same symbols are used. After nucleation a severing protein could clip off the new microtubule and the free minus end would be recognized by CAMSAP/Patronin family members. Depending on the particular family member the minus end could either be stabilized or could grow.