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Published 10 June 2002. doi:10.1083/jcb.200203001
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© The Rockefeller University Press, 0021-9525/2002/6/1041 $5.00
The Journal of Cell Biology, Volume 157, Number 6, June 10, 2002 1041-1048

Article

The adenomatous polyposis coli protein unambiguously localizes to microtubule plus ends and is involved in establishing parallel arrays of microtubule bundles in highly polarized epithelial cells



Mette M. Mogensen1,2,3, John B. Tucker2, John B. Mackie2, Alan R. Prescott1 and Inke S. Näthke1

1 School of Life Sciences, University of Dundee, Dundee DD1 5 EH, United Kingdom
2 School of Biology, Bute Medical Building, University of St. Andrews, Fife KY16 9TS, United Kingdom
3 School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, United Kingdom

Address correspondence to Inke S. Näthke, School of Life Sciences, University of Dundee, WTB/MSI Complex, Dow St., Dundee DD1 5 EH, United Kingdom. Tel.: 44-1382-345821. Fax: 44-1382-345386. E-mail: i.s.nathke{at}dundee.ac.uk

Loss of full-length adenomatous polyposis coli (APC) protein correlates with the development of colon cancers in familial and sporadic cases. In addition to its role in regulating ß-catenin levels in the Wnt signaling pathway, the APC protein is implicated in regulating cytoskeletal organization. APC stabilizes microtubules in vivo and in vitro, and this may play a role in cell migration (Näthke, I.S., C.L. Adams, P. Polakis, J.H. Sellin, and W.J. Nelson. 1996. J. Cell Biol. 134:165–179; Mimori-Kiyosue, Y., N. Shiina, and S. Tsukita. 2000. J. Cell Biol. 148:505–517; Zumbrunn, J., K. Inoshita, A.A. Hyman, and I.S. Näthke. 2001. Curr. Biol. 11:44–49) and in the attachment of microtubules to kinetochores during mitosis (Fodde, R., J. Kuipers, C. Rosenberg, R. Smits, M. Kielman, C. Gaspar, J.H. van Es, C. Breukel, J. Wiegant, R.H. Giles, and H. Clevers. 2001. Nat. Cell Biol. 3:433–438; Kaplan, K.B., A. Burds, J.R. Swedlow, S.S. Bekir, P.K. Sorger, and I.S. Näthke. 2001. Nat. Cell Biol. 3:429–432). The localization of endogenous APC protein is complex: actin- and microtubule-dependent pools of APC have been identified in cultured cells (Näthke et al., 1996; Mimori-Kiyosue et al., 2000; Reinacher-Schick, A., and B.M. Gumbiner. 2001. J. Cell Biol. 152:491–502; Rosin-Arbesfeld, R., G. Ihrke, and M. Bienz. 2001. EMBO J. 20:5929–5939). However, the localization of APC in tissues has not been identified at high resolution. Here, we show that in fully polarized epithelial cells from the inner ear, endogenous APC protein associates with the plus ends of microtubules located at the basal plasma membrane. Consistent with a role for APC in supporting the cytoskeletal organization of epithelial cells in vivo, the number of microtubules is significantly reduced in apico-basal arrays of microtubule bundles isolated from mice heterozygous for APC.

Key Words: microtubule organization; microtubule hook decoration; cytoskeleton; cochlea; min mouse


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