Ankyrin-G induces nucleoporin Nup358 to associate with the axon initial segment of neurons

J Cell Sci. 2019 Sep 26;132(18):jcs222802. doi: 10.1242/jcs.222802.

Abstract

Nup358 (also known as RanBP2) is a member of the large nucleoporin family that constitutes the nuclear pore complex. Depending on the cell type and the physiological state, Nup358 interacts with specific partner proteins and influences distinct mechanisms independent of its role in nucleocytoplasmic transport. Here, we provide evidence that Nup358 associates selectively with the axon initial segment (AIS) of mature neurons, mediated by the AIS scaffold protein ankyrin-G (AnkG, also known as Ank3). The N-terminus of Nup358 is demonstrated to be sufficient for its localization at the AIS. Further, we show that Nup358 is expressed as two isoforms, one full-length and another shorter form of Nup358. These isoforms differ in their subcellular distribution in neurons and expression level during neuronal development. Overall, the present study highlights an unprecedented localization of Nup358 within the AIS and suggests its involvement in neuronal function.This article has an associated First Person interview with the first author of the paper.

Keywords: Ankyrin-G; Axon initial segment; Nucleoporin; Nup358; RanBP2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ankyrins / genetics
  • Ankyrins / metabolism*
  • Axons / metabolism*
  • Blotting, Western
  • Embryo, Mammalian / metabolism*
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Mice
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Neurons / metabolism*
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism

Substances

  • Ank3 protein, mouse
  • Ankyrins
  • Molecular Chaperones
  • Nuclear Pore Complex Proteins
  • Protein Isoforms
  • ran-binding protein 2