Acid-sensing ion channel (ASIC) 4 predominantly localizes to an early endosome-related organelle upon heterologous expression

Sci Rep. 2015 Dec 15;5:18242. doi: 10.1038/srep18242.

Abstract

Acid-sensing ion channels (ASICs) are voltage-independent proton-gated amiloride sensitive sodium channels, belonging to the DEG/ENaC gene family. Six different ASICs have been identified (ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, ASIC4) that are activated by a drop in extracellular pH, either as homo- or heteromers. An exception is ASIC4, which is not activated by protons as a homomer and which does not contribute to functional heteromeric ASICs. Insensitivity of ASIC4 to protons and its comparatively low sequence identity to other ASICs (45%) raises the question whether ASIC4 may have different functions than other ASICs. In this study, we therefore investigated the subcellular localization of ASIC4 in heterologous cell lines, which revealed a surprising accumulation of the channel in early endosome-related vacuoles. Moreover, we identified an unique amino-terminal motif as important for forward-trafficking from the ER/Golgi to the early endosome-related compartment. Collectively, our results show that heterologously expressed ASIC4 predominantly resides in an intracellular endosomal compartment.

MeSH terms

  • Acid Sensing Ion Channels / chemistry
  • Acid Sensing Ion Channels / genetics*
  • Acid Sensing Ion Channels / metabolism*
  • Amino Acid Motifs
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Endosomes / metabolism*
  • Gene Expression*
  • HEK293 Cells
  • Humans
  • Intracellular Space
  • Lysosomes / metabolism
  • Mutation
  • Protein Interaction Domains and Motifs
  • Protein Transport
  • Transport Vesicles / metabolism

Substances

  • Acid Sensing Ion Channels