Microtubule Anchoring: Attaching Dynamic Polymers to Cellular Structures

Abstract

Microtubules are dynamic, filamentous polymers composed of α- and β-tubulin. Arrays of microtubules that have a specific polarity and distribution mediate essential processes such as intracellular transport and mitotic chromosome segregation. Microtubule arrays are generated with the help of microtubule organizing centers (MTOC). MTOCs typically combine two principal activities, the de novo formation of microtubules, termed nucleation, and the immobilization of one of the two ends of microtubules, termed anchoring. Nucleation is mediated by the γ-tubulin ring complex (γTuRC), which, in cooperation with its recruitment and activation factors, provides a template for α- and β-tubulin assembly, facilitating formation of microtubule polymer. In contrast, the molecules and mechanisms that anchor newly formed microtubules at MTOCs are less well characterized. Here we discuss the mechanistic challenges underlying microtubule anchoring, how this is linked with the molecular activities of known and proposed anchoring factors, and what consequences defective microtubule anchoring has at the cellular and organismal level.

Keywords: MTOC; anchoring; centrosome; microtubule; nucleation.

FIGURE 1

Overview of microtubule anchoring sites and mechanisms. (A): Conceptual overview of mechanisms by which microtubules can be anchored at MTOCs. From left to right: first, the nucleator may be part of the anchoring complex as a stabilizing minus-end cap. Anchoring to the MTOC may be achieved through an MTOC-bound adapter that interacts with the minus-end cap or with the microtubule lattice. Lattice interaction could be direct or indirect via a minus-end directed motor. Second, the nucleator may not be part of the anchoring complex. In this case anchoring is facilitated by an adapter protein interacting with a minus-end-bound, stabilizing protein. (B–E): Examples of MTOCs and associated anchoring factors. (B): At the interphase centrosome anchoring to the mother centriole is achieved through multiple mechanisms, involving ninein-dynein at the subdistal appendages, FSD1 in the central region, and MSD1-WDR8 in the proximal/PCM region. FSD1-and MSD1-mediated anchoring may be transient and minus-ends may be transferred to subdistal appendages. (C): Anchoring at cis-Golgi membranes involves the AKAP9-myomegalin complex as adapter and CAMSAP2 as stabilizer at the microtubule minus-end that connects it to the adapter complex. EB proteins provide an additional way of connecting microtubules to the adapter complex through myomegalin. (D): At apical junction complexes and membranes in epithelial cells both ninein- and CAMSAP-mediated anchoring mechanisms may act in parallel. (E): At branch points on plant cortical microtubules, MSD1-WDR8 complexes stabilize and anchor the minus-ends of newly nucleated microtubule branches to the lattice of the pre-existing microtubules.