title: TACC3 is a microtubule plus end-tracking protein that promotes axon elongation and also regulates microtubule plus end dynamics in multiple embryonic cell types.
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.
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA 02467.
authors.forename: Belinda U
authors.initials: BU
authors.lastname: Nwagbara
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA 02467.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Faris
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA 02467.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Bearce
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA 02467.
authors.forename: Burcu
authors.initials: B
authors.lastname: Erdogan
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA 02467.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Ebbert
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA 02467.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Evans
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA 02467.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Rutherford
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA 02467.
authors.forename: Tiffany B
authors.initials: TB
authors.lastname: Enzenbacher
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA 02467 Laura.lowery@bc.edu.
authors.forename: Laura Anne
authors.initials: LA
authors.lastname: Lowery
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D046149:Embryo Culture Techniques; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism; D007399:Interphase; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology
chemical_list: C486738:CKAP5 protein, Xenopus; D008869:Microtubule-Associated Proteins; C474872:TACC3 protein, Xenopus; D014157:Transcription Factors; D029867:Xenopus Proteins