Abstract
Ceramide, a key signaling sphingolipid in the plasma membrane, plays a pivotal role in fundamental cellular processes such as adhesion, polarity, and programmed cell death. The generation of plasma membrane ceramide is largely attributed to the activity of two types of sphingomyelinases: neutral sphingomyelinase 2 (nSMase2, Smpd3) and acid sphingomyelinase (aSMase, Smpd1). While many studies have explored ceramide generation following experimental activation of these enzymes, the mechanisms governing basal or steady- state ceramide levels have remained poorly understood. Using an innovative mass spectrometry approach developed in the Canals’ lab, the team has quantified the distinct contributions of nSMase2 and aSMase to plasma membrane ceramide homeostasis. Remarkably, their findings reveal that nSMase2 is the primary driver of ceramide regulation in the plasma membrane, establishing its critical role in maintaining ceramide homeostasis and signaling under physiological conditions.
Document Type
Article
Publication Date
2-2025
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.jlr.2024.100737
Funding Information
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health Grant/award numbers R01AG064234, R21AG078601, RF1AG078338.
Repository Citation
Quadri, Zainuddin and Bieberich, Erhard, "Staying sane in the membrane: Neutral sphingomyelinase 2 as a master regulator of plasma membrane ceramide" (2025). Markey Cancer Center Faculty Publications. 403.
https://uknowledge.uky.edu/markey_facpub/403
Notes/Citation Information
© 2024 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).