Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2.
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.
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
Peter T
PT
Ruane
Division of Cell Biology, Faculty of Science, University of Utrecht, Padualaan 8, 3584CH, Utrecht, The Netherlands.
Laura F
LF
Gumy
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
Becky
B
Bola
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
Beverley
B
Anderson
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
Marcin J
MJ
Wozniak
Division of Cell Biology, Faculty of Science, University of Utrecht, Padualaan 8, 3584CH, Utrecht, The Netherlands.
Casper C
CC
Hoogenraad
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
Victoria J
VJ
Allan
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000502:physiology*
D025601:Adenomatous Polyposis Coli Protein; C509805:KIF2A protein, human; C488101:KIF5B protein, human; D016547:Kinesins