Neutral sphingomyelinases control extracellular vesicles budding from the plasma membrane

Journal of extracellular vesicles - Tập 6 Số 1 - 2017
Kerstin Menck1,2, Can Sönmezer3, Thomas Worst4,5, Matthias Schulz1, Gry H. Dihazi6, Frank Streit6, Gerrit Erdmann7, Simon Kling8, Michael Boutros5, Claudia R. Binder1, Julia Christina Gross3
1Hematology and Oncology, University Medical Center Goettingen, Goettingen, Germany
2INSERM, U1068, Centre de Recherche en Cancérologie de Marseille Institut Paoli‐Calmettes, CNRS UMR7258, and Université Aix‐Marseille Marseille France
3Hematology and Oncology/Developmental Biochemistry, University Medical Center Goettingen, Goettingen, Germany
4Department of Urology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany
5Division Signaling and Functional Genomics, German Cancer Research Center (DKFZ) and Heidelberg University, Heidelberg, Germany
6Department of Clinical Chemistry, University Medical Center Goettingen, Goettingen, Germany
7NMI TT Pharmaservices, Berlin, Germany
8NMI Natural and Medical Sciences Institute, University of Tübingen, Reutlingen, Germany

Tóm tắt

ABSTRACTExtracellular vesicles (EVs) are membrane particles secreted from cells into all body fluids. Several EV populations exist differing in size and cellular origin. Using differential centrifugation EVs pelleting at 14,000 g (“microvesicles” (MV)) and 100,000 g (“exosomes”) are distinguishable by protein markers. Neutral sphingomyelinase (nSMase) inhibition has been shown to inhibit exosome release from cells and has since been used to study their functional implications. How nSMases (also known as SMPD2 and SMPD3) affect the basal secretion of MVs is unclear. Here we investigated how SMPD2/3 impact both EV populations. SMPD2/3 inhibition by GW4869 or RNAi decreases secretion of exosomes, but also increases secretion of MVs from the plasma membrane. Both populations differ significantly in metabolite composition and Wnt proteins are specifically loaded onto MVs under these conditions. Taken together, our data reveal a novel regulatory function of SMPD2/3 in vesicle budding from the plasma membrane and clearly suggest that – despite the different vesicle biogenesis – the routes of vesicular export are adaptable.

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Journal of extracellular vesicles

Tập 6 Số 1

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