TMEM184B modulates endolysosomal acidification via the vesicular proton pump

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Endolysosomal acidification is critical for neuronal function, and its disruption is linked to neurodevelopmental and neurodegenerative disorders.
• The precise molecular mechanisms governing neuronal endolysosomal pH regulation are not fully understood.
• Transmembrane protein 184B (TMEM184B), essential for synaptic function, has been implicated in neurodevelopmental disorders.

Purpose of the Study:

• To identify key regulators of neuronal endolysosomal pH.
• To elucidate the role of TMEM184B in endolysosomal acidification and its connection to neurological disorders.

Main Methods:

• Localization studies of TMEM184B within neuronal cells.
• Proteomic analysis to identify TMEM184B interacting partners.
• Comparative analysis of endolysosomal acidification in Tmem184b-mutant and wild-type mouse neurons.
• Assessment of vacuolar ATPase (V-ATPase) complex assembly in mouse brains.

Main Results:

• TMEM184B localizes to early and late endosomes and interacts with the V-ATPase complex.
• Tmem184b-mutant neurons exhibit significantly reduced endolysosomal acidification.
• V-ATPase complex assembly is diminished in Tmem184b-mutant mouse brains.
• TMEM184B appears to promote V-ATPase activity, facilitating endosomal flux.

Conclusions:

• TMEM184B is identified as a crucial regulator of neuronal endolysosomal acidification.
• The findings provide a mechanistic link between TMEM184B function, V-ATPase activity, and neuronal health.
• This study offers insights into the pathophysiology of TMEM184B-associated nervous system disorders.