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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 - Mol. Biol. Cell (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Boston College, Chestnut Hill, MA 02467.

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Cartoon schematic of proposed model of TACC3 interaction at MT plus ends. Both TACC3 (red) and XMAP215 (green) bind to the extreme MT plus end. TACC3 and XMAP215 are known to interact with each other through their C-terminal domains (Lee et al., 2001; Thakur et al., 2014), whereas XMAP215 can bind to tubulin dimers through its N-terminal TOG domains (Widlund et al., 2011). TACC3 and XMAP215 complex formation in the cytoplasm may serve to stabilize each other (Bellanger and Gonczy, 2003; Figure 7), and TACC3 interaction with XMAP215 may promote more efficient binding of the complex to MTs in order to drive MT polymerization activity (Kinoshita et al., 2005; Peset et al., 2005). It is unknown whether TACC3 can bind to MT plus ends directly or only through XMAP215 (as depicted here). EB1 (orange) binding to MT plus ends is behind TACC3 and XMAP215 (Figure 6). Not drawn to scale.
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Figure 8: Cartoon schematic of proposed model of TACC3 interaction at MT plus ends. Both TACC3 (red) and XMAP215 (green) bind to the extreme MT plus end. TACC3 and XMAP215 are known to interact with each other through their C-terminal domains (Lee et al., 2001; Thakur et al., 2014), whereas XMAP215 can bind to tubulin dimers through its N-terminal TOG domains (Widlund et al., 2011). TACC3 and XMAP215 complex formation in the cytoplasm may serve to stabilize each other (Bellanger and Gonczy, 2003; Figure 7), and TACC3 interaction with XMAP215 may promote more efficient binding of the complex to MTs in order to drive MT polymerization activity (Kinoshita et al., 2005; Peset et al., 2005). It is unknown whether TACC3 can bind to MT plus ends directly or only through XMAP215 (as depicted here). EB1 (orange) binding to MT plus ends is behind TACC3 and XMAP215 (Figure 6). Not drawn to scale.

Mentions: Evidence suggests that the TACC3-XMAP215 complex may generally be more stable than either protein individually, as each of them affects the protein level of the other in Xenopus whole-embryo lysates. This is consistent with studies in Caenorhabditis elegans showing that normal levels of TACC3 and XMAP215 orthologues are required to maintain the overall cytoplasmic signal of the other (Bellanger and Gonczy, 2003). Taken together, our data combined with others suggest a model in which XMAP215 and TACC3 form a complex in the cytoplasm that reduces protein turnover and also may increase their binding efficiency to MT plus ends, thus driving more effective MT polymerization (Figure 8). However, we also note that Xenopus TACC3 was first identified as a protein (originally named Maskin) that associates with CPEB to regulate translation in the oocyte (Stebbins-Boaz et al., 1999), and so it is also possible that TACC3 could be regulating XMAP215 protein synthesis rather than, or in addition to, protein stability.


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 - Mol. Biol. Cell (2014)

Cartoon schematic of proposed model of TACC3 interaction at MT plus ends. Both TACC3 (red) and XMAP215 (green) bind to the extreme MT plus end. TACC3 and XMAP215 are known to interact with each other through their C-terminal domains (Lee et al., 2001; Thakur et al., 2014), whereas XMAP215 can bind to tubulin dimers through its N-terminal TOG domains (Widlund et al., 2011). TACC3 and XMAP215 complex formation in the cytoplasm may serve to stabilize each other (Bellanger and Gonczy, 2003; Figure 7), and TACC3 interaction with XMAP215 may promote more efficient binding of the complex to MTs in order to drive MT polymerization activity (Kinoshita et al., 2005; Peset et al., 2005). It is unknown whether TACC3 can bind to MT plus ends directly or only through XMAP215 (as depicted here). EB1 (orange) binding to MT plus ends is behind TACC3 and XMAP215 (Figure 6). Not drawn to scale.
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Related In: Results  -  Collection

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Figure 8: Cartoon schematic of proposed model of TACC3 interaction at MT plus ends. Both TACC3 (red) and XMAP215 (green) bind to the extreme MT plus end. TACC3 and XMAP215 are known to interact with each other through their C-terminal domains (Lee et al., 2001; Thakur et al., 2014), whereas XMAP215 can bind to tubulin dimers through its N-terminal TOG domains (Widlund et al., 2011). TACC3 and XMAP215 complex formation in the cytoplasm may serve to stabilize each other (Bellanger and Gonczy, 2003; Figure 7), and TACC3 interaction with XMAP215 may promote more efficient binding of the complex to MTs in order to drive MT polymerization activity (Kinoshita et al., 2005; Peset et al., 2005). It is unknown whether TACC3 can bind to MT plus ends directly or only through XMAP215 (as depicted here). EB1 (orange) binding to MT plus ends is behind TACC3 and XMAP215 (Figure 6). Not drawn to scale.
Mentions: Evidence suggests that the TACC3-XMAP215 complex may generally be more stable than either protein individually, as each of them affects the protein level of the other in Xenopus whole-embryo lysates. This is consistent with studies in Caenorhabditis elegans showing that normal levels of TACC3 and XMAP215 orthologues are required to maintain the overall cytoplasmic signal of the other (Bellanger and Gonczy, 2003). Taken together, our data combined with others suggest a model in which XMAP215 and TACC3 form a complex in the cytoplasm that reduces protein turnover and also may increase their binding efficiency to MT plus ends, thus driving more effective MT polymerization (Figure 8). However, we also note that Xenopus TACC3 was first identified as a protein (originally named Maskin) that associates with CPEB to regulate translation in the oocyte (Stebbins-Boaz et al., 1999), and so it is also possible that TACC3 could be regulating XMAP215 protein synthesis rather than, or in addition to, protein stability.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Boston College, Chestnut Hill, MA 02467.

Show MeSH
Related in: MedlinePlus