XB-ART-51327
Mol Biol Cell
November 1, 2014;
25
(21):
3350-62.
TACC3 is a microtubule plus end-tracking protein that promotes axon elongation and also regulates microtubule plus end dynamics in multiple embryonic cell types.
Nwagbara BU
,
Faris AE
,
Bearce EA
,
Erdogan B
,
Ebbert PT
,
Evans MF
,
Rutherford EL
,
Enzenbacher TB
,
Lowery LA
.
Abstract
Microtubule plus end dynamics are regulated by a conserved family of proteins called plus end-tracking proteins (+TIPs). It is unclear how various +TIPs interact with each other and with plus ends to control microtubule behavior. The centrosome-associated protein TACC3, a member of the transforming acidic coiled-coil (TACC) domain family, has been implicated in regulating several aspects of microtubule dynamics. However, TACC3 has not been shown to function as a +TIP in vertebrates. Here we show that TACC3 promotes axon outgrowth and regulates microtubule dynamics by increasing microtubule plus end velocities in vivo. We also demonstrate that TACC3 acts as a +TIP in multiple embryonic cell types and that this requires the conserved C-terminal TACC domain. Using high-resolution live-imaging data on tagged +TIPs, we show that TACC3 localizes to the extreme microtubule plus end, where it lies distal to the microtubule polymerization marker EB1 and directly overlaps with the microtubule polymerase XMAP215. TACC3 also plays a role in regulating XMAP215 stability and localizing XMAP215 to microtubule plus ends. Taken together, our results implicate TACC3 as a +TIP that functions with XMAP215 to regulate microtubule plus end dynamics.
PubMed ID: 25187649
PMC ID: PMC4214782
Article link: Mol Biol Cell
Grant support: [+]
R00 MH095768 NIMH NIH HHS
Species referenced: Xenopus laevis
Genes referenced: ckap5 gnl3 mapre1 slc12a3 tacc3
Antibodies: Tacc3 Ab2
Morpholinos: tacc3 MO2
Article Images: [+] show captions
References [+] :
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Xie, Cep120 and TACCs control interkinetic nuclear migration and the neural progenitor pool. 2007, Pubmed
Yang, DOCK7 interacts with TACC3 to regulate interkinetic nuclear migration and cortical neurogenesis. 2012, Pubmed
Zhou, NGF-induced axon growth is mediated by localized inactivation of GSK-3beta and functions of the microtubule plus end binding protein APC. 2004, Pubmed
van der Vaart, SLAIN2 links microtubule plus end-tracking proteins and controls microtubule growth in interphase. 2011, Pubmed
van der Vaart, Microtubule plus-end tracking proteins SLAIN1/2 and ch-TOG promote axonal development. 2012, Pubmed
Applegate, plusTipTracker: Quantitative image analysis software for the measurement of microtubule dynamics. 2011, Pubmed
Barnard, Differential phosphorylation controls Maskin association with eukaryotic translation initiation factor 4E and localization on the mitotic apparatus. 2005, Pubmed , Xenbase
Bellanger, TAC-1 and ZYG-9 form a complex that promotes microtubule assembly in C. elegans embryos. 2003, Pubmed
Brouhard, XMAP215 is a processive microtubule polymerase. 2008, Pubmed , Xenbase
Cullen, Msps protein is localized to acentrosomal poles to ensure bipolarity of Drosophila meiotic spindles. 2001, Pubmed
Engel, Abelson phosphorylation of CLASP2 modulates its association with microtubules and actin. 2014, Pubmed , Xenbase
Gergely, D-TACC: a novel centrosomal protein required for normal spindle function in the early Drosophila embryo. 2000, Pubmed
Gergely, The TACC domain identifies a family of centrosomal proteins that can interact with microtubules. 2001, Pubmed
Giet, Drosophila Aurora A kinase is required to localize D-TACC to centrosomes and to regulate astral microtubules. 2002, Pubmed , Xenbase
Groisman, CPEB, maskin, and cyclin B1 mRNA at the mitotic apparatus: implications for local translational control of cell division. 2000, Pubmed , Xenbase
Gómez, Working with Xenopus spinal neurons in live cell culture. 2003, Pubmed , Xenbase
Honnappa, An EB1-binding motif acts as a microtubule tip localization signal. 2009, Pubmed
Hur, GSK3 controls axon growth via CLASP-mediated regulation of growth cone microtubules. 2011, Pubmed
Kinoshita, Aurora A phosphorylation of TACC3/maskin is required for centrosome-dependent microtubule assembly in mitosis. 2005, Pubmed , Xenbase
Le Bot, TAC-1, a regulator of microtubule length in the C. elegans embryo. 2003, Pubmed
Lee, The microtubule plus end tracking protein Orbit/MAST/CLASP acts downstream of the tyrosine kinase Abl in mediating axon guidance. 2004, Pubmed , Xenbase
Lee, Msps/XMAP215 interacts with the centrosomal protein D-TACC to regulate microtubule behaviour. 2001, Pubmed , Xenbase
Li, EB1 promotes microtubule dynamics by recruiting Sentin in Drosophila cells. 2011, Pubmed
Long, Multiparametric analysis of CLASP-interacting protein functions during interphase microtubule dynamics. 2013, Pubmed , Xenbase
Lowery, Growth cone-specific functions of XMAP215 in restricting microtubule dynamics and promoting axonal outgrowth. 2013, Pubmed , Xenbase
Lowery, The trip of the tip: understanding the growth cone machinery. 2009, Pubmed , Xenbase
Marx, Xenopus cytoplasmic linker-associated protein 1 (XCLASP1) promotes axon elongation and advance of pioneer microtubules. 2013, Pubmed , Xenbase
Maurer, EB1 accelerates two conformational transitions important for microtubule maturation and dynamics. 2014, Pubmed
Nakamura, Dissecting the nanoscale distributions and functions of microtubule-end-binding proteins EB1 and ch-TOG in interphase HeLa cells. 2012, Pubmed
Neukirchen, Cytoplasmic linker proteins regulate neuronal polarization through microtubule and growth cone dynamics. 2011, Pubmed
O'Brien, The Xenopus TACC homologue, maskin, functions in mitotic spindle assembly. 2005, Pubmed , Xenbase
Peset, The TACC proteins: TACC-ling microtubule dynamics and centrosome function. 2008, Pubmed
Peset, Function and regulation of Maskin, a TACC family protein, in microtubule growth during mitosis. 2005, Pubmed , Xenbase
Rochlin, Microtubule stability decreases axon elongation but not axoplasm production. 1996, Pubmed
Sadek, TACC3 expression is tightly regulated during early differentiation. 2003, Pubmed
Samereier, Analysis of Dictyostelium TACC reveals differential interactions with CP224 and unusual dynamics of Dictyostelium microtubules. 2011, Pubmed
Shcherbo, Far-red fluorescent tags for protein imaging in living tissues. 2009, Pubmed , Xenbase
Sive, Microinjection of Xenopus embryos. 2010, Pubmed , Xenbase
Srayko, Caenorhabditis elegans TAC-1 and ZYG-9 form a complex that is essential for long astral and spindle microtubules. 2003, Pubmed
Stebbins-Boaz, Maskin is a CPEB-associated factor that transiently interacts with elF-4E. 2000, Pubmed , Xenbase
Stepanova, Visualization of microtubule growth in cultured neurons via the use of EB3-GFP (end-binding protein 3-green fluorescent protein). 2003, Pubmed
Stout, Using plusTipTracker software to measure microtubule dynamics in Xenopus laevis growth cones. 2014, Pubmed , Xenbase
Tanaka, Microtubule behavior in the growth cones of living neurons during axon elongation. 1991, Pubmed , Xenbase
Tanaka, The role of microtubule dynamics in growth cone motility and axonal growth. 1995, Pubmed , Xenbase
Tessmar, A screen for co-factors of Six3. 2002, Pubmed , Xenbase
Thakur, The centrosomal adaptor TACC3 and the microtubule polymerase chTOG interact via defined C-terminal subdomains in an Aurora-A kinase-independent manner. 2014, Pubmed
Widlund, XMAP215 polymerase activity is built by combining multiple tubulin-binding TOG domains and a basic lattice-binding region. 2011, Pubmed
Xie, Cep120 and TACCs control interkinetic nuclear migration and the neural progenitor pool. 2007, Pubmed
Yang, DOCK7 interacts with TACC3 to regulate interkinetic nuclear migration and cortical neurogenesis. 2012, Pubmed
Zhou, NGF-induced axon growth is mediated by localized inactivation of GSK-3beta and functions of the microtubule plus end binding protein APC. 2004, Pubmed
van der Vaart, SLAIN2 links microtubule plus end-tracking proteins and controls microtubule growth in interphase. 2011, Pubmed
van der Vaart, Microtubule plus-end tracking proteins SLAIN1/2 and ch-TOG promote axonal development. 2012, Pubmed