{"entity": "researcher", "timestamp": "2026-11-06T04:13:53.516Z", "family": "Kirschbaum", "given": "Carla", "initials": "C", "orcid": "0000-0003-3192-0785", "affiliations": ["Department of Chemistry, Dorothy Crowfoot Hodgkin Building, University of Oxford, Oxford, UK."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/998da12d50d84ffd8da720613bc6a63b.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/998da12d50d84ffd8da720613bc6a63b"}}, "publications": [{"entity": "publication", "iuid": "b3dc70afbc154ba7b862610edb3cabeb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b3dc70afbc154ba7b862610edb3cabeb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b3dc70afbc154ba7b862610edb3cabeb"}}, "title": "Structure of NHE6 and its lipid-mediated interactions regulating endosomal pH.", "authors": [{"family": "Jung", "given": "Sukkyeong", "initials": "S", "orcid": "0000-0002-4730-5245", "researcher": {"href": "https://publications.scilifelab.se/researcher/f65f769bad8a4fd6a4186b7ddaaf6051.json"}}, {"family": "Yeo", "given": "Hyunku", "initials": "H", "orcid": "0000-0002-8701-8902", "researcher": {"href": "https://publications.scilifelab.se/researcher/d2361cbef9ee454898183a56a0cbb9a8.json"}}, {"family": "Li", "given": "Hang", "initials": "H"}, {"family": "Kokane", "given": "Surabhi", "initials": "S"}, {"family": "Reichenbach", "given": "Tom", "initials": "T"}, {"family": "Gulati", "given": "Ashutosh", "initials": "A", "orcid": "0000-0003-0960-994X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a0b2b0aa7260492c8141083762e08125.json"}}, {"family": "Albano", "given": "Giuseppe", "initials": "G"}, {"family": "Kirschbaum", "given": "Carla", "initials": "C", "orcid": "0000-0003-3192-0785", "researcher": {"href": "https://publications.scilifelab.se/researcher/998da12d50d84ffd8da720613bc6a63b.json"}}, {"family": "Ho", "given": "Tin Manh", "initials": "TM", "orcid": "0000-0003-1608-2234", "researcher": {"href": "https://publications.scilifelab.se/researcher/72472dd6ef684f17ab462e5064b2203d.json"}}, {"family": "Landreh", "given": "Michael", "initials": "M", "orcid": "0000-0002-7958-4074", "researcher": {"href": "https://publications.scilifelab.se/researcher/87494f4204c04be9bce5e9ddcdc92d8a.json"}}, {"family": "Abramsson", "given": "Mia", "initials": "M", "orcid": "0000-0002-8184-0145", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b13d2ef38bf49d386f12ad170ae939d.json"}}, {"family": "Robinson", "given": "Carol V", "initials": "CV", "orcid": "0000-0001-7829-5505", "researcher": {"href": "https://publications.scilifelab.se/researcher/109418b5455b4a32bcff02b54d49885b.json"}}, {"family": "Fuster", "given": "Daniel G", "initials": "DG"}, {"family": "Drew", "given": "David", "initials": "D", "orcid": "0000-0001-8866-6349", "researcher": {"href": "https://publications.scilifelab.se/researcher/cc19844f8147480fb0af2e437744131b.json"}}], "type": "journal article", "published": "2026-08-11", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "17", "issue": "1", "issn-l": "2041-1723"}, "abstract": "Sodium-proton exchangers (NHEs) are found in all cells to regulate intracellular pH, sodium levels and cell volume. In humans, there are nine different NHE transporters (SLC9A1-9), which vary in tissue distribution, kinetics and regulation. NHE6 localizes to endosomal membranes and mutations in the protein are known to cause the X-linked neurological disorder Christianson syndrome. Despite its importance, the structural basis of NHE6 function and regulation is unclear. Here we report four cryo-electron microscopy structures of rat NHE6 between 2.2 and 3.3 \u00c5 resolution, revealing its homodimeric structure, ion binding and remodelling by lipids. We characterize a lipid-binding site between the protomers that accommodates the endosomal-specific phosphatidylinositol 3-phosphate (PI3P) lipid. Using solid-supported membrane (SSM)-based electrophysiology we demonstrate that NHE6 transports both Na+ and K+ ions and that PI3P enhances NHE6 stability and activity. Furthermore, we identify a phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) lipid, which interacts with the C-terminal domain of NHE6 to stabilize an auto-inhibited state. We further demonstrate that NHE6 is non-functional when mislocalized to the plasma membrane where PI(4,5)P2 is primarily located. We propose the lipid-dependent regulation has evolved to shut-down NHE6 activity during recycling of endosomes at the plasma membrane.", "doi": "10.1038/s41467-026-75877-x", "pmid": "42581050", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13463026"}, {"db": "pii", "key": "10.1038/s41467-026-75877-x"}], "notes": [], "created": "2026-11-05T15:02:33.717Z", "modified": "2026-11-05T15:02:33.899Z"}]}