Differential effects of N-glycans on surface expression suggest structural differences between acid-sensing ion channel (ASIC) 1a and ASIC1b

Ivan Kadurin , Andjelko Golubovic , Lilia Leisle , Hermann Schindelin , Stefan Gründer (1)

1 Institute of Physiology

Acid-sensing ion channels (ASICs) are H+-gated Na+ channels, with a widespread expression pattern in the central and the peripheral nervous system. ASICs have a simple topology with two transmembrane domains, cytoplasmic termini, and a large ectodomain between the transmembrane domains; this topology has been confirmed by the crystal structure of chicken ASIC. ASIC1a and ASIC1b are two variants encoded by the asic1 gene. The variable part of the protein includes the cytoplasmic N-terminus, the first transmembrane domain and approximately the first third of the ectodomain. Both variants contain two consensus sequences for N-linked glycosylation in the common, distal part of the ectodomain. In contrast to ASIC1a, ASIC1b contains two additional consensus sequences in the variable, proximal part of the ectodomain. Here we show that all extracellular Asn residues within putative consensus sequences for N-glycosylation carry glycans. The two common, distal glycans increase surface expression of the channels but are no absolute requirement for channel activity. In sharp contrast, the presence of at least one of the two proximal glycans, which are specific to ASIC1b, is an absolute requirement for surface expression of ASIC1b. This result suggests substantial differences in the structure of the proximal ectodomain between the two ASIC1 variants.

Mots clés: Life Sciences

Ivan Kadurin, Andjelko Golubovic, Lilia Leisle, Hermann Schindelin, Stefan Gründer. Differential effects of N-glycans on surface expression suggest structural differences between acid-sensing ion channel (ASIC) 1a and ASIC1b. Biochemical Journal, 2008, 412 (3), pp.469-475. ⟨10.1042/BJ20071614⟩. ⟨hal-00478927⟩