Role of Nonmotor Microtubule‐Associated Proteins in Mitotic Spindle Assembly

Abstract

The assembly of a microtubule (MT)‐based bipolar spindle is a distinct hallmark of mitosis. Mitotic spindle assembly is tightly controlled in order to ensure proper chromosome attachment and segregation during mitosis. This regulation is achieved by the coordinated action of many motor and nonmotor MT‐associated proteins (MAPs). Owing to the distinctive capacity of MAPs to associate with the MT minus and/or plus ends, as well as with the MT lattice, they play an essential role in the spatial and temporal regulation of MT behaviour during mitotic spindle assembly.

Key Concepts

  • The mitotic spindle is a dynamic structure composed of microtubules, motor and nonmotor proteins.
  • Proper chromosome alignment and segregation during mitosis requires bipolar spindle assembly.
  • Nonmotor microtubule‐associated proteins are involved in spindle pole focusing, microtubule dynamics, kinetochore‐microtubule attachment stability and cytokinesis.
  • Nonmotor microtubule‐associated proteins associate with microtubule plus and minus ends (+TIPs and −TIPs, respectively) as well as with the microtubule lattice.
  • Nonmotor microtubule‐associated proteins are tightly regulated during the cell cycle.

Keywords: mitosis; mitotic spindle; microtubule; microtubule dynamics; microtubule‐associated proteins; +TIPs; −TIPs

Figure 1. Nonmotor MAPs decorate KTs, spindle MTs and spindle poles during mitosis. Immunofluorescence of HeLa cells labelled with antibodies against different nonmotor MAPs. ChTOG, NuMA and TPX2 localise at the spindle poles during mitosis, regulating spindle pole formation and focusing. CLASPs, CLIP and Astrin are +TIPs that localise at the KTs and play major role in dynamics and stability of KT‐MT attachments. Spindle MTs are labelled in red, DNA (deoxyribonucleic acid) is in blue and MAPs in green. Scale bar is 5 µm.
Figure 2. Nonmotor MAPs associate with MT plus and minus ends (+TIPs and −TIPs, respectively). (A) EB proteins decorate the plus ends of growing MTs protecting them from depolymerisation. (B) CLIPs bind MTs through a CAP‐Gly domain and regulate KT‐MT attachments. (C) XMAP215/chTOG is a tubulin polymerase. During mitosis, it concentrates at centrosomes where it plays a major role in MT stabilisation and spindle pole organisation. (D) CLASPs are a family of +TIPs important for the regulation of MT dynamics at KTs and throughout the spindle. (E) Astrin decorates MT plus ends and KTs on bi‐oriented chromosomes. Thus, the presence of the Astrin/SKAP complex on KTs serves as good marker for stable end‐on KT‐MT attachments. (F) CAMSAPs are a family of MT minus‐end tracking proteins involved in MT minus end stabilisation. (G) NuMA is a protein required for spindle pole formation and focusing. (H) NuMA localisation at the polar region plays an important role in spindle orientation. Its interaction with the cell cortex is established through the N‐terminal domain of LGN that further interacts with Gα1 at the cell cortex. (I) MCRS1 decorates a small area at the distal parts of K‐fibres, where it regulates MT minus‐end dynamics. (J) ASP/ASPM localises to the minus ends of spindle MT bundles and plays an important role in spindle MT cross‐linking and focusing.
Figure 3. The role of lattice‐associated nonmotor MAPs in spindle assembly. (A) During mitosis, TPX2 regulates spindle pole formation and proper Aurora A localisation at the mitotic spindle. Moreover, TPX2 function at the spindle pole is also regulated through phosphorylation by Aurora A. (B) HURP is a nonmotor MAP associated with K‐fibres, with a higher concentration closer to the chromosomes, where it plays an important role in the stabilisation of K‐fibres. (C) PRC1 is a nonmotor MAP that can bind antiparallel MTs and plays an important role during mitotic exit and cytokinesis.
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Further Reading

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Drpic, Danica, and Maiato, Helder(Jul 2017) Role of Nonmotor Microtubule‐Associated Proteins in Mitotic Spindle Assembly. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022520]