Adenomatous polyposis coli on microtubule plus ends in cell extensions can promote microtubule net growth with or without EB1.

Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Molecular Biology of the Cell (Impact Factor: 4.47). 06/2006; 17(5):2331-45. DOI: 10.1091/mbc.E05-06-0498
Source: PubMed


In interphase cells, the adenomatous polyposis coli (APC) protein accumulates on a small subset of microtubules (MTs) in cell protrusions, suggesting that APC may regulate the dynamics of these MTs. We comicroinjected a nonperturbing fluorescently labeled monoclonal antibody and labeled tubulin to simultaneously visualize dynamics of endogenous APC and MTs in living cells. MTs decorated with APC spent more time growing and had a decreased catastrophe frequency compared with non-APC-decorated MTs. Endogenous APC associated briefly with shortening MTs. To determine the relationship between APC and its binding partner EB1, we monitored EB1-green fluorescent protein and endogenous APC concomitantly in living cells. Only a small fraction of EB1 colocalized with APC at any one time. APC-deficient cells and EB1 small interfering RNA showed that EB1 and APC localized at MT ends independently. Depletion of EB1 did not change the growth-stabilizing effects of APC on MT plus ends. In addition, APC remained bound to MTs stabilized with low nocodazole, whereas EB1 did not. Thus, we demonstrate that the association of endogenous APC with MT ends correlates directly with their increased growth stability, that this can occur independently of its association with EB1, and that APC and EB1 can associate with MT plus ends by distinct mechanisms.

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    • "Could the MT phenotype be explained by the failure of Kif3a deficient cells to target APC to MT tips? Similar to our findings, non APC-decorated MTs are characterized by a decreased growth rate and by increased pausing [35]. In addition, migration is impaired in APC depleted cells [36]. "
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    • "Similarly, the contribution of APC to the regulation of cytoskeletal proteins, particularly microtubules and actin, is well established (Moseley et al., 2007; Munemitsu et al., 1994; Näthke et al., 1996; Okada et al., 2010; Smith et al., 1994). The changes in cytoskeletal organization and processes associated with microtubules and actin, including migration and cell division that accompany APC loss, have been described by many research groups (Caldwell et al., 2007; Dikovskaya et al., 2010; Dikovskaya et al., 2004; Dikovskaya et al., 2007; Green et al., 2005; Green and Kaplan, 2003; Kita et al., 2006; Kroboth et al., 2007; Marshall et al., 2011). In the context of cancer, changes in these interactions of APC cause cells to migrate less efficiently and to increase their residence time in the challenging environment of the intestinal tract (Nelson "

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