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Contact-dependent incorporation of endoplasmic reticulum into retraction fibers and migrasomes

Peiyao Fan1, Rui Ji1,2, Yiling Wen1

  • 1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Institute of Advanced Clinical Medicine, Peking University, Beijing, China.

The Journal of Cell Biology
|November 6, 2025
PubMed

Insights

Migrating cells use tubular endoplasmic reticulum (ER) within retraction fibers to deliver cholesterol and calcium to migrasomes. This ER network facilitates long-range signaling and migrasome development in moving cells.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biophysics

Background:

  • Migrating cells form retraction fibers (RFs) and migrasomes at their rear.
  • Migrasomes are crucial for extracellular signaling but their connection to the cell body via RFs suggests intracellular roles.
  • The mechanism for localized signaling molecule transport through RFs to migrasomes is not fully understood.

Purpose of the Study:

  • To investigate the role of tubular endoplasmic reticulum (ER) in migrasome formation and function.
  • To elucidate the mechanism of long-range signal transmission via RFs and migrasomes.
  • To understand how cellular components are transported to migrasomes.

Main Methods:

  • Microscopy to visualize ER dynamics in RFs and migrasomes.
  • Investigating microtubule regulation of ER extension.
  • Analyzing ER-plasma membrane contact sites (ER-PM MCSs) in relation to migrasomes.

Main Results:

  • Tubular ER extends into RFs and localizes to migrasomes, dependent on microtubule regulation.
  • ER adheres to migrasome sites via ER-PM MCSs.
  • Tubular ER acts as a reservoir for cholesterol and calcium, transferring these molecules to migrasomes, potentially promoting membrane stability and secretion.

Conclusions:

  • Tubular ER exhibits novel dynamics within RFs, extending to migrasomes.
  • ER-PM MCSs are critical for ER tethering and molecule transfer to migrasomes.
  • This study reveals a new mechanism for long-range, site-specific transport of calcium and cholesterol via ER, RFs, and migrasomes in migrating cells.

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