Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2.pdf (6.24 MB)
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Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2.

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posted on 23.05.2018, 14:47 by Peter T. Ruane, Laura F. Gumy, Becky Bola, Beverley Anderson, Marcin J. Wozniak, Casper C. Hoogenraad, Victoria J. Allan
Microtubules and their associated proteins (MAPs) underpin the polarity of specialised cells. Adenomatous polyposis coli (APC) is one such MAP with a multifunctional agenda that requires precise intracellular localisations. Although APC has been found to associate with kinesin-2 subfamily members, the exact mechanism for the peripheral localization of APC remains unclear. Here we show that the heavy chain of kinesin-1 directly interacts with the APC C-terminus, contributing to the peripheral localisation of APC in fibroblasts. In rat hippocampal neurons the kinesin-1 binding domain of APC is required for its axon tip enrichment. Moreover, we demonstrate that APC requires interactions with both kinesin-2 and kinesin-1 for this localisation. Underlining the importance of the kinesin-1 association, neurons expressing APC lacking kinesin-1-binding domain have shorter axons. The identification of this novel kinesin-1-APC interaction highlights the complexity and significance of APC localisation in neurons.

Funding

This work was funded by The Biotechnology and Biological Sciences Research Council (grants BB/G012652/1 and BB/H017828/1), The Wellcome Trust (GR075373MA, WT078825AIA and 097820/Z/11/Z), and FP7 EU Marie Curie postdoctoral intra-European fellowship (L.F.G: MDPTAR 272156), Netherlands Organization for Scientific Research (L.F.G. and C.C.H.: 821.02.005). The Bioimaging Facility Leica SP8 microscope used in this study was purchased by the University of Manchester. Special thanks goes to Peter March for his help with the SP8 microscopy.

History

Citation

Scientific Reports,2016, 6, Article number: 27456

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

Version

VoR (Version of Record)

Published in

Scientific Reports

Publisher

Nature Publishing Group

issn

2045-2322

eissn

2045-2322

Acceptance date

17/05/2016

Copyright date

2016

Available date

23/05/2018

Publisher version

https://www.nature.com/articles/srep27456

Notes

Supplementary information accompanies this paper at http://www.nature.com/srep

Language

en