Endoplasmic reticulum–plasma membrane contact gradients direct cell migration

Bo Gong (), Jake D. Johnston, Alexander Thiemicke, Alex Marco and Tobias Meyer ()
Additional contact information
Bo Gong: Weill Cornell Medicine
Jake D. Johnston: Columbia University
Alexander Thiemicke: Weill Cornell Medicine
Alex Marco: New York Structural Biology Center
Tobias Meyer: Weill Cornell Medicine

Nature, 2024, vol. 631, issue 8020, 415-423

Abstract: Abstract Directed cell migration is driven by the front–back polarization of intracellular signalling1–3. Receptor tyrosine kinases and other inputs activate local signals that trigger membrane protrusions at the front2,4–6. Equally important is a long-range inhibitory mechanism that suppresses signalling at the back to prevent the formation of multiple fronts7–9. However, the identity of this mechanism is unknown. Here we report that endoplasmic reticulum–plasma membrane (ER–PM) contact sites are polarized in single and collectively migrating cells. The increased density of these ER–PM contacts at the back provides the ER-resident PTP1B phosphatase more access to PM substrates, which confines receptor signalling to the front and directs cell migration. Polarization of the ER–PM contacts is due to microtubule-regulated polarization of the ER, with more RTN4-rich curved ER at the front and more CLIMP63-rich flattened ER at the back. The resulting ER curvature gradient leads to small and unstable ER–PM contacts only at the front. These contacts flow backwards and grow to large and stable contacts at the back to form the front–back ER–PM contact gradient. Together, our study suggests that the structural polarity mediated by ER–PM contact gradients polarizes cell signalling, directs cell migration and prolongs cell migration.

Date: 2024
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-024-07527-5 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:631:y:2024:i:8020:d:10.1038_s41586-024-07527-5

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-024-07527-5

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().