Sphingosine Kinase 1 Cooperates with Autophagy to Maintain Endocytic Membrane Trafficking

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Sphingosine kinase 1 (Sphk1) associates with early endocytic membranes during endocytosis; however, the role of sphingosine or sphingosine-1-phosphate as the critical metabolite in endocytic trafficking has not been established. Here, we demonstrate that the recruitment of Sphk1 to sphingosine-enriched endocytic vesicles and the generation of sphingosine-1-phosphate facilitate membrane trafficking along the endosomal pathway. Exogenous sphingosine and sphingosine-based Sphk1 inhibitors induce the Sphk1-dependent fusion of endosomal membranes to accumulate enlarged late endosomes and amphisomes enriched in sphingolipids. Interestingly, Sphk1 also appears to facilitate endosomal fusion independent of its catalytic activity, given that catalytically inactive Sphk1G82D is recruited to endocytic membranes by sphingosine or sphingosine-based Sphk1 inhibitor and promotes membrane fusion. Furthermore, we reveal that the clearance of enlarged endosomes is dependent on the activity of ceramide synthase, lysosomal biogenesis, and the restoration of autophagic flux. Collectively, these studies uncover intersecting roles for Sphk1, sphingosine, and autophagic machinery in endocytic membrane trafficking.

Original languageEnglish (US)
Pages (from-to)1532-1545
Number of pages14
JournalCell Reports
Volume17
Issue number6
DOIs
StatePublished - Nov 1 2016

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Sphingosine
Autophagy
Membranes
Membrane Fusion
Fusion reactions
Endosomes
Transport Vesicles
Sphingolipids
Metabolites
Endocytosis
sphingosine kinase
Restoration
Machinery
Catalyst activity
Fluxes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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title = "Sphingosine Kinase 1 Cooperates with Autophagy to Maintain Endocytic Membrane Trafficking",
abstract = "Sphingosine kinase 1 (Sphk1) associates with early endocytic membranes during endocytosis; however, the role of sphingosine or sphingosine-1-phosphate as the critical metabolite in endocytic trafficking has not been established. Here, we demonstrate that the recruitment of Sphk1 to sphingosine-enriched endocytic vesicles and the generation of sphingosine-1-phosphate facilitate membrane trafficking along the endosomal pathway. Exogenous sphingosine and sphingosine-based Sphk1 inhibitors induce the Sphk1-dependent fusion of endosomal membranes to accumulate enlarged late endosomes and amphisomes enriched in sphingolipids. Interestingly, Sphk1 also appears to facilitate endosomal fusion independent of its catalytic activity, given that catalytically inactive Sphk1G82D is recruited to endocytic membranes by sphingosine or sphingosine-based Sphk1 inhibitor and promotes membrane fusion. Furthermore, we reveal that the clearance of enlarged endosomes is dependent on the activity of ceramide synthase, lysosomal biogenesis, and the restoration of autophagic flux. Collectively, these studies uncover intersecting roles for Sphk1, sphingosine, and autophagic machinery in endocytic membrane trafficking.",
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Sphingosine Kinase 1 Cooperates with Autophagy to Maintain Endocytic Membrane Trafficking. / Young, Megan Marie; Takahashi, Yoshinori; Fox, Todd E.; Yun, Jong; Kester, Mark; Wang, Hong-Gang.

In: Cell Reports, Vol. 17, No. 6, 01.11.2016, p. 1532-1545.

Research output: Contribution to journalArticle

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