APC nuclear membrane association and microtubule polarity.
BACKGROUND
Directional cell migration is a fundamental feature of embryonic development, the inflammatory response and the metastatic spread of cancer. Migrating cells have a polarized morphology with an asymmetric distribution of signalling molecules and of the actin and microtubule cytoskeletons. The dynamic reorganization of the actin cytoskeleton provides the major driving force for migration in all mammalian cell types, but microtubules also play an important role in many cells, most notably neuronal precursors.


RESULTS
We previously showed, using primary fibroblasts and astrocytes in in vitro scratch-induced migration assays, that the accumulation of APC (adenomatous polyposis coli; the APC tumour suppressor protein) at microtubule plus-ends promotes their association with the plasma membrane at the leading edge. This is required for polarization of the microtubule cytoskeleton during directional migration. Here, we have examined the organization of microtubules in the soma of migrating neurons and fibroblasts.


CONCLUSIONS
We find that APC, through a direct interaction with the NPC (nuclear pore complex) protein Nup153 (nucleoporin 153), promotes the association of microtubules with the nuclear membrane.
MRC Laboratory for Molecular Cell Biology, Cancer Research UK Oncogene and Signal Transduction Group and Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.
Ludovic
L
Collin
Karni
K
Schlessinger
Alan
A
Hall
D011125:Adenomatous Polyposis Coli; D025601:Adenomatous Polyposis Coli Protein / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000166:cytology; D018929:Cell Culture Techniques; D002465:Cell Movement; D016764:Cell Polarity; D018385:Centrosome / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D008870:Microtubules / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism*; D022022:Nuclear Pore / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017384:Sequence Deletion
D025601:Adenomatous Polyposis Coli Protein; C079377:NUP153 protein, human; D028861:Nuclear Pore Complex Proteins