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Updated: Jun 4, 2025

A Fluorescence-based Assay of Phospholipid Scramblase Activity
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A Fluorescence-based Assay of Phospholipid Scramblase Activity

Published on: September 20, 2016

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Membrane structure-responsive lipid scramblase activity of the TMEM63/OSCA family

Yugo Miyata1, Megumi Nishimura1, Aya Nagata1

  • 1Department of Medical Chemistry, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo, Japan.

FEBS Letters
|December 23, 2024
PubMed

Insights

Vertebrate TMEM63B orthologs function as membrane structure-responsive scramblases, disrupting plasma membrane phospholipid asymmetry. This scramblase activity is conserved across species and linked to pathogenic variants.

Area of Science:

  • Cell Biology
  • Membrane Biology
  • Biochemistry

Background:

  • Phospholipids are asymmetrically distributed in the plasma membrane (PM).
  • Scramblases are proteins that disrupt this asymmetry by shuffling phospholipids.
  • Mouse Tmem63b was recently identified as a membrane structure-responsive scramblase belonging to the TMEM63/OSCA family of ion channels.

Purpose of the Study:

  • To investigate the conservation of scramblase activity within the TMEM63/OSCA family.
  • To determine if TMEM63B orthologs from vertebrates exhibit scramblase activity.
  • To analyze the functional consequences of human TMEM63B variants on scramblase activity.

Main Methods:

  • Expression of human TMEM63 paralogs, TMEM63B orthologs, and plant OSCA1.1 in Tmem63b-deficient mouse pro-B cells.
  • Functional assessment of scramblase activity at the plasma membrane.
  • Analysis of ten previously identified pathogenic human TMEM63B variants.

Main Results:

  • Vertebrate TMEM63B orthologs demonstrated scramblase activity at the plasma membrane.
  • Nine out of ten pathogenic human TMEM63B variants exhibited constitutive scramblase activity.
  • Scramblase activity at the PM is conserved among vertebrate TMEM63B orthologs.

Conclusions:

  • The membrane structure-responsive scramblase activity of TMEM63b is conserved in vertebrate TMEM63B orthologs.
  • Pathogenic TMEM63B variants frequently display constitutive scramblase activity, highlighting the importance of regulated phospholipid asymmetry.
Keywords:
ion channelmechanotransductionneurodegenerationphospholipidplasma membranescramblase

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