title: Acid-sensing ion channel (ASIC) 4 predominantly localizes to an early endosome-related organelle upon heterologous expression.
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.
authors.affiliation: Institute of Physiology, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Schwartz
authors.affiliation: Institute of Physiology, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Friedrich
authors.affiliation: Institute of Physiology, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Polleichtner
authors.affiliation: Institute of Physiology, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gründer
mesh_terms: D062565:Acid Sensing Ion Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020816:Amino Acid Motifs; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D011992:Endosomes / Q000378:metabolism*; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space; D008247:Lysosomes / Q000378:metabolism; D009154:Mutation; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: D062565:Acid Sensing Ion Channels