The armadillo protein p0071 controls KIF3 motor transport

J Cell Sci. 2017 Oct 1;130(19):3374-3387. doi: 10.1242/jcs.200170. Epub 2017 Aug 14.

Abstract

We here report a novel function of the armadillo protein p0071 (also known as PKP4) during transport mediated by the KIF3 transport complex. Secretion of chromogranin A and matrix metallopeptidase 9 from pancreatic neuroendocrine tumor cells or pancreatic cancer cells, respectively, was substantially reduced following knockdown of p0071. Vesicle tracking indicated that there was impaired directional persistence of vesicle movement upon p0071 depletion. This suggests a disturbed balance between plus- and minus-end directed microtubule transport in cells lacking p0071. p0071 directly interacts with the KIF3 motor subunit KIF3B. Our data indicate that p0071 also interacts with the kinesin cargo adaptor protein KAP3 (also known as KIFAP3) acting as a stabilizing linker between KIF3B and its KAP3 cargo-binding entity. Thus, p0071 is required for directional vesicle movement and secretion of different KIF3-transported carriers, thereby regulating the transport of intracellular membrane vesicles along microtubules.

Keywords: Chromogranin; KIF3; Kinesin-2; MMP9; Protein transport; p0071.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Kinesins / genetics
  • Kinesins / metabolism*
  • Plakophilins / genetics
  • Plakophilins / metabolism*
  • Protein Transport / physiology
  • Secretory Vesicles / genetics
  • Secretory Vesicles / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • KIF3A protein, human
  • KIFAP3 protein, human
  • PKP4 protein, human
  • Plakophilins
  • Kinesins