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Updated: Mar 27, 2026

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
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MCTP1 and MCTP2 promote ER-PM contact sites and regulate PI4P homeostasis and cell migration

Suganthan Amirthagunanathan1, Maxime Boutry2, Vasudeva Tati1

  • 1Department of Biochemistry and Cell and Molecular Biology, University of Tennessee at Knoxville, Knoxville, TN 37916.

Molecular Biology of the Cell
|March 25, 2026
PubMed

Insights

Membrane contact proteins MCTP1 and MCTP2 regulate endoplasmic reticulum-plasma membrane (ER-PM) interactions. They control lipid homeostasis and cell migration by binding phosphoinositides at ER-PM contact sites.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Endoplasmic reticulum-plasma membrane (ER-PM) contact sites are crucial for cellular lipid and calcium homeostasis, as well as cell signaling.
  • Multiple organelles interact with the ER at specialized membrane contact sites (MCS).

Purpose of the Study:

  • To identify proteins involved in ER-organelle MCS.
  • To investigate the role of the transmembrane proteins MCTP1 and MCTP2 in ER-PM contact sites and their regulation of cellular processes.

Main Methods:

  • Proximity labeling assays were used to identify proteins at ER subdomains forming MCS with other organelles.
  • Overexpression and gene deletion strategies were employed to study the function of MCTPs.
  • Biochemical assays were performed to analyze the binding of MCTP C2 domains to phosphoinositides.

Main Results:

  • MCTP1 and MCTP2 were localized to ER subdomains that form MCS with multiple organelles.
  • Overexpression of MCTPs enhanced ER-PM contact sites in a C2 domain-dependent manner.
  • MCTP C2 domains bind to PI(4)P and PI(4,5)P2, phosphoinositides enriched in the PM.
  • Deletion of MCTP1 or MCTP2 led to increased PI(4)P levels at the PM and promoted cell migration.

Conclusions:

  • MCTPs are identified as proteins mediating contact between the ER and multiple organelles.
  • MCTPs play a significant role at ER-PM contact sites, regulating lipid homeostasis and cell migration.

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