Mini-review: Microtubule sliding in neurons

Abstract

Microtubule sliding is an underappreciated mechanism that contributes to the establishment, organization, preservation, and plasticity of neuronal microtubule arrays. Powered by molecular motor proteins and regulated in part by static crosslinker proteins, microtubule sliding is the movement of microtubules relative to other microtubules or to non-microtubule structures such as the actin cytoskeleton. In addition to other important functions, microtubule sliding significantly contributes to the establishment and maintenance of microtubule polarity patterns in different regions of the neuron. The purpose of this article is to review the state of knowledge on microtubule sliding in the neuron, with emphasis on its mechanistic underpinnings as well as its functional significance.

Keywords: Axon; Cytoplasmic dynein; KIFC1; Kinesin-1; Microtubule; Microtubule crosslinking; Microtubule polarity orientation; Microtubule polarity sorting; Microtubule sliding; Microtubule transport; TRIM46.

Figure 1.

Hypothetical microtubule (MT) array expanded by either microtubule assembly alone, microtubule sliding alone or a combination of the two together.

Figure 2.

Theoretical demonstration of how motor-based microtubule (MT) sliding can affect microtubule distribution and organization. Panel A shows how a plus-end-directed motor adhered to less moveable substrate (such as a glass coverslip) causes a microtubule to move with minus-end leading, while a minus-end-directed motor causes a microtubule to move with plus-end leading. Panel B illustrates various hypothetical arrangements of microtubules moving relative to other microtubules via (i) a plus-end directed motor or (ii) a minus-end directed motor. The microtubules are driven with different ends leading, depending on the motor and whether the microtubules are parallel (the same orientation) or anti-parallel (opposite orientations). Movements result from most or all of the motors having their motor domain on the same microtubule of the two. Non-movements result from equal numbers of motors having their motor domain on each of the two microtubules. Elements of this figure were inspired by [26].

Figure 3.

Schematic illustrations of how a dynein-driven microtubule-polarity sorting mechanism observed experimentally on glass coverslips (panel A) can function in the axon to generate and preserve a nearly uniform plus-end-out pattern of microtubule polarity orientation by selectively transporting minus-end-out microtubules retrogradely into the cell body. Elements of this figure were inspired by [30, 35].

Figure 4.

Schematic depiction of how static microtubule crosslinkers function in the axon to tamp down potential movements of long microtubules. Shown is a hypothetical dimeric crosslinker with a microtubule-binding domain and a projection domain. Due to its ability to pivot, the crosslinker can crosslink either parallel or anti-parallel microtubules. Short microtubules remain mobile because they are unlikely to have a crosslink immobilize them. Shown also is a severing event (by katanin or spastin) that creates short potentially mobile microtubules by cutting them from the longer immobile ones.

Figure 5.

Mechanistic model for various factors contributing to the motor-driven polarity sorting of microtubules in the axon. The upper part of the figure schematically illustrates how the various factors shown in the lower part of the figure contribute to generate or regulate microtubule movements in the axon. The lower part of the figure shows in the form of a table the relevant players, their properties, their role, and the experimental evidence supporting the model. Elements of this figure were inspired by [30, 35]. Kinesin-6 motors are not included in the schematic because they act at the level of the cell body, not within the axon itself.