Tumour Suppressor Adenomatous Polyposis Coli (APC) Localisation Is Regulated by Both Kinesin-1 and Kinesin-2

Sci Rep. 2016 Jun 7;6:27456. doi: 10.1038/srep27456.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli / genetics*
  • Adenomatous Polyposis Coli Protein / genetics*
  • Genes, Tumor Suppressor*
  • HeLa Cells
  • Humans
  • Kinesin / physiology*

Substances

  • Adenomatous Polyposis Coli Protein
  • KIF2A protein, human
  • KIF5B protein, human
  • Kinesin