Document Type
Article
Publication Date
5-29-2019
Publication Title
Biology Open
Volume
8
Issue
10
First page number:
1
Last page number:
56
Abstract
In human, loss of acid sphingomyelinase (ASM/SMPD1) causes Niemann–Pick disease, type A. ASM hydrolyzes sphingomyelins to produce ceramides but protein targets of ASM remain largely unclear. Our mass spectrometry-based proteomic analyses have identified >100 proteins associated with the ASM-dependent, detergent-resistant membrane microdomains (lipid rafts), with >60% of these proteins being palmitoylated, including SNAP23, Src-family kinases Yes and Lyn, and Ras and Rab family small GTPases. Inactivation of ASM abolished the presence of these proteins in the plasma membrane, with many of them trapped in the Golgi. While palmitoylation inhibitors and palmitoylation mutants phenocopied the effects of ASM inactivation, we demonstrated that ASM is required for the transport of palmitoylated proteins, such as SNAP23 and Lyn, from the Golgi to the plasma membrane without affecting palmitoylation directly. Importantly, ASM delivered extracellularly can regulate the trafficking of SNAP23 from the Golgi to the plasma membrane. Our studies suggest that ASM, acting at the plasma membrane to produce ceramides, regulates the localization and trafficking of the palmitoylated proteins.
Keywords
Acid sphingomyelinase; Ceramide; Lipid raft; Proteomics; Protein palmitoylation; Protien trafficking; Plasa membrane; Golgi
Disciplines
Biochemistry, Biophysics, and Structural Biology
File Format
File Size
6720 KB
Language
English
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Repository Citation
Xiong, X.,
Lee, C.,
Li, W.,
Yu, J.,
Zhu, L.,
Kim, Y.,
Zhang, H.,
Sun, H.
(2019).
Acid Sphingomyelinase Regulates the Localization and Trafficking of Palmitoylated Proteins.
Biology Open, 8(10),
1-56.
http://dx.doi.org/10.1242/bio.040311
