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Endosomal chloride/proton exchangers need inhibitory TMEM9 β-subunits for regulation and prevention of disease-causing overactivity

ABSTRACT: Multi-epitope affinity purification mass spectrometry (meAP-MS) analysis of TMEM9-, TMEM9B- and CLC3- associated proteins from solubilized mouse brain membranes identified chloride channel subtypes CLCN3, 4 and 5 as exclusive interaction partners of TMEM9 and TMM9B.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Alexander Haupt

LAB HEAD: Prof. Dr. Bernd Fakler

PROVIDER: PXD061285 | Pride | 2025-05-07

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	mousebrain-KO-Tmem9-CL47-T9AC2-gp1.mzId	Mzid
	mousebrain-KO-Tmem9-CL47-T9AC2-gp1_o.mgf	Mgf
	mousebrain-KO-Tmem9-CL47-T9AC2-gp1_o.raw	Raw
	mousebrain-KO-Tmem9-CL47-T9AC2-gp1_u.mgf	Mgf
	mousebrain-KO-Tmem9-CL47-T9AC2-gp1_u.raw	Raw

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Publications

Endosomal chloride/proton exchangers need inhibitory TMEM9 β-subunits for regulation and prevention of disease-causing overactivity.

Planells-Cases Rosa R Vorobeva Viktoriia V Kar Sumanta S Schmitt Franziska W FW Schulte Uwe U Schrecker Marina M Hite Richard K RK Fakler Bernd B Jentsch Thomas J TJ

Nature communications 20250401 1

The function of endosomes critically depends on their ion homeostasis. A crucial role of luminal Cl<sup>-</sup>, in addition to that of H<sup>+</sup>, is increasingly recognized. Both ions are transported by five distinct endolysosomal CLC chloride/proton exchangers. Dysfunction of each of these transporters entails severe disease. Here we identified TMEM9 and TMEM9B as obligatory β-subunits for endosomal ClC-3, ClC-4, and ClC-5. Mice lacking both β-subunits displayed severely reduced levels of ...[more]

PMID: 40169677

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