CLASP Suppresses Microtubule Catastrophes through a Single TOG Domain

Amol Aher, Maurits Kok, Ashwani Sharma, Ankit Rai, Natacha Olieric, Ruddi Rodriguez-Garcia, Eugene A Katrukha, Tobias Weinert, Vincent Olieric, Lukas C Kapitein, Michel O Steinmetz, Marileen Dogterom, Anna Akhmanova

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The dynamic instability of microtubules plays a key role in controlling their organization and function, but the cellular mechanisms regulating this process are poorly understood. Here, we show that cytoplasmic linker-associated proteins (CLASPs) suppress transitions from microtubule growth to shortening, termed catastrophes, including those induced by microtubule-destabilizing agents and physical barriers. Mammalian CLASPs encompass three TOG-like domains, TOG1, TOG2, and TOG3, none of which bind to free tubulin. TOG2 is essential for catastrophe suppression, whereas TOG3 mildly enhances rescues but cannot suppress catastrophes. These functions are inhibited by the C-terminal domain of CLASP2, while the TOG1 domain can release this auto-inhibition. TOG2 fused to a positively charged microtubule-binding peptide autonomously accumulates at growing but not shrinking ends, suppresses catastrophes, and stimulates rescues. CLASPs suppress catastrophes by stabilizing growing microtubule ends, including incomplete ones, preventing their depolymerization and promoting their recovery into complete tubes. TOG2 domain is the key determinant of these activities.

Original languageEnglish
Pages (from-to)40-58.e8
JournalDevelopmental Cell
Volume46
Issue number1
DOIs
Publication statusPublished - 2 Jul 2018

Keywords

  • Animals
  • Binding Sites
  • COS Cells
  • Cell Line
  • Cell Proliferation/physiology
  • Cercopithecus aethiops
  • HEK293 Cells
  • Humans
  • Microtubule-Associated Proteins/genetics
  • Microtubules/metabolism
  • Protein Binding
  • Protein Domains/physiology
  • Spindle Apparatus/metabolism
  • Tubulin/metabolism

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