Nup358 interacts with APC and plays a role in cell polarization.
Asymmetric localization of adenomatous polyposis coli (APC) to the ends of a subset of microtubules located in the leading edges is essential for the establishment of front-rear polarity during cell migration. APC is known to associate with microtubules in three ways: through interaction with the plus-end tracking protein EB1, direct binding through a C-terminal basic region, and through interaction with the plus-end motor kinesin-2. Here we report that the middle region of APC has a previously unidentified microtubule plus-end-targeting function, suggesting an additional microtubule-binding mode for APC. Through the same region, APC interacts with Nup358 (also called RanBP2), a microtubule-binding nucleoporin. Ectopic expression of the middle region of APC is sufficient to recruit endogenous Nup358 to the plus ends of microtubules. Furthermore, our results indicate that Nup358 cooperates with kinesin-2 to regulate the localization of APC to the cell cortex through a nuclear-transport-independent mechanism. Using RNA interference and a scratch-induced wound-healing assay we demonstrate that Nup358 functions in polarized cell migration. These results reveal a more active role for structural nucleoporins in regulating fundamental cellular processes than previously anticipated.
Murawala
Prayag
P
National Centre for Cell Science, Pune, India.
Tripathi
Mukesh Mani
MM
Vyas
Pankhuri
P
Salunke
Aparna
A
Joseph
Jomon
J
D025601:Adenomatous Polyposis Coli Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D016764:Cell Polarity; D006801:Humans; D008870:Microtubules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport
D025601:Adenomatous Polyposis Coli Protein; D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; C094493:ran-binding protein 2