CLASP Suppresses Microtubule Catastrophes through a Single TOG Domain
| العنوان: | CLASP Suppresses Microtubule Catastrophes through a Single TOG Domain |
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| المؤلفون: | Aher, Amol, Kok, Maurits, Sharma, Ashwani, Rai, Ankit, Olieric, Natacha, Rodriguez-Garcia, Ruddi, Katrukha, Eugene A, Weinert, Tobias, Olieric, Vincent, Kapitein, Lukas C, Steinmetz, Michel O, Dogterom, Marileen, Akhmanova, Anna, Celbiologie, Sub Cell Biology |
| المساهمون: | Celbiologie, Sub Cell Biology |
| المصدر: | Developmental Cell Developmental Cell, 46(1), 40. Cell Press Developmental Cell, 46(1) |
| بيانات النشر: | Cell Press, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Models, Molecular, single-molecule biophysics, Plasma protein binding, Microtubules, CLIP-170, 0302 clinical medicine, Chlorocebus aethiops, microfabricated barriers, Spindle Apparatus/metabolism, COS cells, biology, EB3, microtubule dynamics, CLASP, Cell biology, EB1, Microtubules/metabolism, COS Cells, Protein Domains/physiology, Microtubule-Associated Proteins, Protein Binding, Cell Proliferation/physiology, Spindle Apparatus, General Biochemistry, Genetics and Molecular Biology, Article, Cell Line, Cercopithecus aethiops, 03 medical and health sciences, Protein Domains, Microtubule, Animals, Humans, Amino Acid Sequence, Binding site, Molecular Biology, Cell Proliferation, X-ray crystallography, TOG domain, Binding Sites, HEK 293 cells, Cell Biology, Tubulin/metabolism, Microtubule-Associated Proteins/genetics, 030104 developmental biology, Tubulin, HEK293 Cells, tubulin, Cytoplasm, biology.protein, 030217 neurology & neurosurgery, Function (biology), Developmental Biology |
| الوصف: | Summary 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 Highlights • CLASPs potently suppress microtubule catastrophes induced by different mechanisms • CLASPs act by stabilizing growing microtubule ends, including incomplete ones • CLASP2 TOG-like domain, TOG2, is necessary and sufficient for catastrophe inhibition • TOG2 fused to a positively charged peptide accumulates at growing microtubule ends 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. |
| وصف الملف: | image/pdf; application/pdf |
| اللغة: | English |
| تدمد: | 1878-1551 1534-5807 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e26d2c41a1456df7962f2dc02f31b040Test http://europepmc.org/articles/PMC6035287Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e26d2c41a1456df7962f2dc02f31b040 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18781551 15345807 |
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