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Related Experiment Video

Updated: Nov 25, 2025

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The Ncoa7 locus regulates V-ATPase formation and function, neurodevelopment and behaviour.

Enrico Castroflorio1, Joery den Hoed2, Daria Svistunova2

  • 1MRC Harwell Institute, Harwell Campus, Oxfordshire, OX11 0RD, UK.

Cellular and Molecular Life Sciences : CMLS
|December 19, 2020
PubMed
Summary

Nuclear receptor coactivator 7 (NCOA7) regulates vacuolar (V)-ATPase assembly and function in neurons. Its absence causes neurodevelopmental defects, lysosomal dysfunction, and behavioral issues like anxiety and social deficits in mice.

Keywords:
AutismBehaviourLysosomeMouseNeurodevelopmentNeuronV-ATPase

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Genetics

Background:

  • The Tre2/Bub2/Cdc16 (TBC) protein family, including nuclear receptor coactivator 7 (NCOA7), is linked to neurodevelopmental disorders.
  • The specific function of NCOA7 in the nervous system and its role in disease pathogenesis are largely unknown.

Purpose of the Study:

  • To investigate the molecular function of NCOA7 in neurons.
  • To generate and analyze a novel mouse model lacking Ncoa7 to understand its in vivo consequences.

Main Methods:

  • Interaction studies between NCOA7 and vacuolar (V)-ATPase in the brain.
  • Analysis of neuronal development, lysosomal formation and function in Ncoa7-deficient neurons and mice.
  • Behavioral assessments in Ncoa7 deletion mice.

Main Results:

  • NCOA7 is essential for the proper assembly and activity of the brain's V-ATPase.
  • Ncoa7 deletion leads to altered neuronal development, impaired lysosomal function, and reduced lysosomal markers.
  • Mice lacking Ncoa7 display anxiety and social behavioral deficits.

Conclusions:

  • NCOA7 acts as a critical regulator of V-ATPase in the brain, impacting lysosomal homeostasis, neuronal connectivity, and behavior.
  • This study elucidates a molecular mechanism involving NCOA7 and V-ATPase essential for normal neurodevelopment.