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An Endoplasmic Reticulum ATPase Safeguards Endoplasmic Reticulum Identity by Removing Ectopically Localized

Qing Qin1, Ting Zhao2, Wei Zou2

  • 1National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.

Cell Reports
|November 11, 2020
PubMed

Insights

A P5A ATPase, CATP-8, prevents mitochondrial proteins from mislocalizing to the endoplasmic reticulum (ER), safeguarding ER structure and function. This prevents ER fragmentation and supports dendrite development.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Organelle Biology

Background:

  • Organelle identity relies on precise protein targeting and surveillance mechanisms to remove mistargeted proteins.
  • While mitochondrial surveillance is known, endoplasmic reticulum (ER) surveillance remains less understood.
  • Msp1 is a known mitochondrial membrane protein clearance factor.

Purpose of the Study:

  • To investigate the endoplasmic reticulum (ER) surveillance mechanism for mistargeted proteins.
  • To identify the role of P5A-type ATPase CATP-8 in protein localization and organelle function.
  • To elucidate the function of CATP-8 in preventing ER fragmentation and supporting neuronal development.

Main Methods:

  • Localization studies of CATP-8 to the ER.
  • Analysis of protein mislocalization in catp-8 mutants.
  • Investigating the impact of mislocalized mitochondrial proteins on ER morphology.
  • Assessing the role of CATP-8 in dendrite development and receptor levels.

Main Results:

  • CATP-8, a P5A-type ATPase, removes ectopic mitochondrial tail-anchored (TA) and signal-anchored (SA) proteins from the ER.
  • In catp-8 mutants, mitochondrial fission protein FIS-1 mislocalizes to the ER, causing ER fragmentation via MFF-2 and DRP-1.
  • CATP-8 is crucial for dendrite development, as catp-8 mutants show reduced DMA-1 levels and diminished dendritic arbors.

Conclusions:

  • P5A ATPase CATP-8 acts as a crucial surveillance mechanism on the ER, preventing the accumulation of mistargeted mitochondrial proteins.
  • This function of CATP-8 is essential for maintaining ER morphology and preventing fragmentation.
  • CATP-8 plays a vital role in neuronal development by ensuring proper dendrite formation, partly through regulating DMA-1 levels.

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