| Structural highlights
Function
[CLAP2_HUMAN] Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules. Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2. This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle. Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex.[1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
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.
CLASP Suppresses Microtubule Catastrophes through a Single TOG Domain.,Aher A, Kok M, Sharma A, Rai A, Olieric N, Rodriguez-Garcia R, Katrukha EA, Weinert T, Olieric V, Kapitein LC, Steinmetz MO, Dogterom M, Akhmanova A Dev Cell. 2018 Jun 15. pii: S1534-5807(18)30453-2. doi:, 10.1016/j.devcel.2018.05.032. PMID:29937387[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Akhmanova A, Hoogenraad CC, Drabek K, Stepanova T, Dortland B, Verkerk T, Vermeulen W, Burgering BM, De Zeeuw CI, Grosveld F, Galjart N. Clasps are CLIP-115 and -170 associating proteins involved in the regional regulation of microtubule dynamics in motile fibroblasts. Cell. 2001 Mar 23;104(6):923-35. PMID:11290329
- ↑ Mimori-Kiyosue Y, Grigoriev I, Lansbergen G, Sasaki H, Matsui C, Severin F, Galjart N, Grosveld F, Vorobjev I, Tsukita S, Akhmanova A. CLASP1 and CLASP2 bind to EB1 and regulate microtubule plus-end dynamics at the cell cortex. J Cell Biol. 2005 Jan 3;168(1):141-53. PMID:15631994 doi:10.1083/jcb.200405094
- ↑ Lansbergen G, Grigoriev I, Mimori-Kiyosue Y, Ohtsuka T, Higa S, Kitajima I, Demmers J, Galjart N, Houtsmuller AB, Grosveld F, Akhmanova A. CLASPs attach microtubule plus ends to the cell cortex through a complex with LL5beta. Dev Cell. 2006 Jul;11(1):21-32. PMID:16824950 doi:http://dx.doi.org/S1534-5807(06)00252-8
- ↑ Mimori-Kiyosue Y, Grigoriev I, Sasaki H, Matsui C, Akhmanova A, Tsukita S, Vorobjev I. Mammalian CLASPs are required for mitotic spindle organization and kinetochore alignment. Genes Cells. 2006 Aug;11(8):845-57. PMID:16866869 doi:GTC990
- ↑ Pereira AL, Pereira AJ, Maia AR, Drabek K, Sayas CL, Hergert PJ, Lince-Faria M, Matos I, Duque C, Stepanova T, Rieder CL, Earnshaw WC, Galjart N, Maiato H. Mammalian CLASP1 and CLASP2 cooperate to ensure mitotic fidelity by regulating spindle and kinetochore function. Mol Biol Cell. 2006 Oct;17(10):4526-42. Epub 2006 Aug 16. PMID:16914514 doi:E06-07-0579
- ↑ Efimov A, Kharitonov A, Efimova N, Loncarek J, Miller PM, Andreyeva N, Gleeson P, Galjart N, Maia AR, McLeod IX, Yates JR 3rd, Maiato H, Khodjakov A, Akhmanova A, Kaverina I. Asymmetric CLASP-dependent nucleation of noncentrosomal microtubules at the trans-Golgi network. Dev Cell. 2007 Jun;12(6):917-30. PMID:17543864 doi:10.1016/j.devcel.2007.04.002
- ↑ Zaoui K, Benseddik K, Daou P, Salaun D, Badache A. ErbB2 receptor controls microtubule capture by recruiting ACF7 to the plasma membrane of migrating cells. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18517-22. doi:, 10.1073/pnas.1000975107. Epub 2010 Oct 11. PMID:20937854 doi:10.1073/pnas.1000975107
- ↑ Aher A, Kok M, Sharma A, Rai A, Olieric N, Rodriguez-Garcia R, Katrukha EA, Weinert T, Olieric V, Kapitein LC, Steinmetz MO, Dogterom M, Akhmanova A. CLASP Suppresses Microtubule Catastrophes through a Single TOG Domain. Dev Cell. 2018 Jun 15. pii: S1534-5807(18)30453-2. doi:, 10.1016/j.devcel.2018.05.032. PMID:29937387 doi:http://dx.doi.org/10.1016/j.devcel.2018.05.032
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