Journal Article

FZJ-2026-03875

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png SLC26A11 is an atypical solute carrier with dual transport-channel function mediating lysosomal sulfate transport

Kuhn, B. T. ; Kovermann, P.FZJ* ; Haddad, B.FZJ* ; Rasmussen, T. ; Hove, T. T. ; Bungert-Plümke, S.FZJ* ; Böttcher, B. ; Machtens, J.-P. (Corresponding author)FZJ* ; Fahlke, C. (Corresponding author)FZJ* ; Geertsma, E. R. (Corresponding author)

2026
Springer Nature [London]

This record in other databases:  

Please use a persistent id in citations: doi:10.1038/s41467-026-75749-4

Abstract: Membrane transporters and channels are generally assumed to be based on distinct structural and functional principles. SLC26A11, a solute carrier with high expression levels in the brain, has been proposed to function as either an anion transporter or a channel. Here, we resolve this apparent discrepancy by demonstrating that SLC26A11 is a dual-function protein capable of operating as both a sulfate transporter and a chloride channel. By resolving its structure and combining biochemical studies and molecular dynamics simulations, we show that SLC26A11 exhibits all the hallmarks of a secondary transporter. The mechanistic basis for its selective ion transport identifies the protein as the elusive lysosomal sulfate exporter. Additionally, we demonstrate that SLC26A11 exhibits an uncoupled, channel-like chloride conductance gated by proton:sulfate symport. Our finding that the chloride-conducting state arises from the transport cycle may contribute to the development of therapeutic strategies for treating brain edema, and the identification of its role in lysosome sulfate efflux may provide new approaches to study and treat lysosomal storage diseases.

Note: This work was supported by the Deutsche Forschungsgemeinschaft(DFG, German Research Foundation) as part of the Research Unit 5046grant (FOR5046; project 426950122) to E.R.G. (subproject P1), J.-P.M.(subproject P2), aswell as toChF (subproject P4). Additional support wasprovided by DFG grants 359471283, 456578072, and 525040890 to B.B.(EM facility Würzburg). Computing time on the supercomputer JURECAat Forschungszentrum Jülich was provided by JARA under grant jara0177to J.-P.M. Open Access funding enabled and organized by Projekt DEAL.

---

Contributing Institute(s):

1. Molekular- und Zellphysiologie (IBI-1)

Research Program(s):

1. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)
2. DFG project G:(GEPRIS)426950122 - FOR 5046: Integrative Analyse epithelialer SLC26 Anionentransporter – von der molekularen Struktur zur Pathophysiologie (426950122) (426950122)

---

Database coverage:
; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 15 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---