PXD064977-1

PXD064977 is an original dataset announced via ProteomeXchange.

Title	Transmembrane protein 184B (TMEM184B) promotes endolysosomal acidification through vesicular proton pump regulation
Description	Disruption of endolysosomal acidification is a hallmark of several neurodevelopmental and neurodegenerative disorders. Impaired acidification causes accumulation of toxic protein aggregates and disrupts neuronal homeostasis, yet the molecular mechanisms regulating endolysosomal pH in neurons remain poorly understood. A critical regulator of lumenal acidification is the vacuolar ATPase (VATPase), a proton pump whose activity depends on dynamic assembly of its V0 and V1 subdomains. In this study, we identify transmembrane protein 184B (TMEM184B) as a novel regulator of endolysosomal acidification in neurons. TMEM184B is an evolutionarily conserved 7-pass transmembrane protein required for synaptic structure and function, and sequence variation in TMEM184B causes neurodevelopmental disorders, but the mechanism for this effect is unknown. We performed proteomic analysis of TMEM184B-interacting proteins and identified enrichment of components involved in endosomal trafficking and function, including the V-ATPase. TMEM184B localizes to early and late endosomes, further supporting a role in the endosomal system. Loss of TMEM184B results in significant reductions in endolysosomal acidification within cultured mouse cortical neurons. This alteration in pH is associated with impaired assembly of the V-ATPase V0 and V1 subcomplexes in the TMEM184B mutant mouse brain, suggesting a mechanism by which TMEM184B promotes flux through the endosomal pathway. Overall, these findings identify a new contributor in maintaining endosomal function and provide a mechanistic basis for disrupted neuronal function in human TMEM184B-associated nervous system disorders.
HostingRepository	PRIDE
AnnounceDate	2025-06-17
AnnouncementXML	Submission_2025-06-16_16:20:54.505.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD064977
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Paul Langlais
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-13 01:01:23	ID requested
⏵ 1	2025-06-16 16:20:54	announced

10.6019/PXD064977;

submitter keyword: VATPase,endolysosomal acidification, TMEM184B

Martha Bhattacharya
contact affiliation	Associate Professor of Neuroscience and BIO5 Institute University of Arizona
contact email	marthab1@arizona.edu
lab head
Paul Langlais
contact affiliation	University of Arizona
contact email	langlais@deptofmed.arizona.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064977
     1. Label: PRIDE project
     2. Name: Transmembrane protein 184B (TMEM184B) promotes endolysosomal acidification through vesicular proton pump regulation