title: 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.
authors.affiliation: Wales Heart Research Institute, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Andy K M
authors.initials: AK
authors.lastname: Lam
authors.forename: Antony
authors.initials: A
authors.lastname: Galione
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Lai
authors.forename: Spyros
authors.initials: S
authors.lastname: Zissimopoulos
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D057809:HEK293 Cells; D006801:Humans; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000097903:Two-Pore Channels
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015220:Calcium Channels; C104759:HAX1 protein, human; C407357:TPCN1 protein, human; D000097903:Two-Pore Channels; C530224:TPCN2 protein, human
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