Stomatin organizes laterally segregated membrane microdomains to modulate transmembrane transport and signal transduction
Abstract
Stomatin is a member of the SPFH (Stomatin, Prohibitin, Flotillin, and HflK/C) protein family, and has been proposed to scaffold functional membrane microdomains (FMMs) on the plasma membrane. Functionally, stomatin has been reported to associate with diverse partner proteins and is implicated in various cellular processes. However, the mechanisms by which it organizes FMMs and exerts its regulatory roles remain unclear. Here, we characterize cryo-EM structures of the stomatin complex, revealing a hexadecameric membrane-anchored assembly that resembles an inverted cup. Sixteen SPFH1 domains insert into the cytosolic leaflet, defining an isolated circular membrane microdomain. Proteomic analyses reveal numerous proteins associated with stomatin, including solute carrier transporters, Rab GTPases and integrins. We further show that stomatin oligomerization is required for integrin-regulated directional cell migration. Together, these findings provide a foundation for understanding the basic role of stomatin in FMM organization and its versatile functions in various physiological and pathological processes.
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BibTeX
@article{yan2026stomatin,
title = {{Stomatin organizes laterally segregated membrane microdomains to modulate transmembrane transport and signal transduction}},
author = {Lu Yan and Xinyue Zhou and Meiqi Li and Chenxi Wang and Bailong Xiao and Peng Xi and Peng Zou and Ning Gao},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78250-0},
url = {https://www.nature.com/articles/s41467-026-78250-0},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Stomatin organizes laterally segregated membrane microdomains to modulate transmembrane transport and signal transduction
AU - Lu Yan
AU - Xinyue Zhou
AU - Meiqi Li
AU - Chenxi Wang
AU - Bailong Xiao
AU - Peng Xi
AU - Peng Zou
AU - Ning Gao
PY - 2026
DA - 2026/10/05
JO - Nature Communications
DO - 10.1038/s41467-026-78250-0
UR - https://www.nature.com/articles/s41467-026-78250-0
AB - Stomatin is a member of the SPFH (Stomatin, Prohibitin, Flotillin, and HflK/C) protein family, and has been proposed to scaffold functional membrane microdomains (FMMs) on the plasma membrane. Functionally, stomatin has been reported to associate with diverse partner proteins and is implicated in various cellular processes. However, the mechanisms by which it organizes FMMs and exerts its regulatory roles remain unclear. Here, we characterize cryo-EM structures of the stomatin complex, revealing a hexadecameric membrane-anchored assembly that resembles an inverted cup. Sixteen SPFH1 domains insert into the cytosolic leaflet, defining an isolated circular membrane microdomain. Proteomic analyses reveal numerous proteins associated with stomatin, including solute carrier transporters, Rab GTPases and integrins. We further show that stomatin oligomerization is required for integrin-regulated directional cell migration. Together, these findings provide a foundation for understanding the basic role of stomatin in FMM organization and its versatile functions in various physiological and pathological processes.
SN - 2041-1723
ER -