CLASP Suppresses Microtubule Catastrophes through a Single TOG Domain

Publication date: Available online 21 June 2018
Source:Developmental Cell
Author(s): 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
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.

Graphical abstract

Teaser

Aher et al. dissect the mechanisms underlying the ability of CLASPs, major microtubule-stabilizing factors in interphase and mitosis, to prevent microtubule from switching from growth to shortening. They show that the CLASP domain essential for this function does not bind to free tubulin but directly stabilizes growing microtubule ends.


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