Hax-1 identified as a two-pore channel (TPC)-binding protein

Abstract

Two-pore channels (TPC1-3) are recently identified endolysosomal ion channels. The mechanism by which these channels are regulated at the molecular level is presently unclear. To identify putative protein regulators of TPCs, we performed unbiased transcriptome-wide screens using the yeast two-hybrid technique to identify potential protein-protein interactions with the intracellular domains of human TPC2. We now present biochemical evidence for a novel molecular interaction between human TPC1/2 and the anti-apoptotic protein Hax-1 (HCLS-associated X-1). The observed binding of Hax-1 to TPCs may represent a conserved mechanism by which these endolysosomal ion channels are regulated.

Keywords: AD; GST; HCLS-associated X-1; IP(3); Lysosomal ion channel; NAADP; PI(3,5)P(2); Protein–protein interactions; SERCA; TM; Two-pore channel; activation domain; glutathione S-transferase; inositol trisphosphate; nicotinic acid adenine dinucleotide phosphate; phosphoinositide-3,5-bisphosphate; sarcoplasmic reticulum Ca(2+)-ATPase; transmembrane.