Cell News 01/2017
13
Neutral sphingomyolinases control Extracellular Vesicles
budding from the plasma membrane
Kerstin Menck, Can Sönmezer, Thomas Stefan Worst, Matthias Schulz, Gry Dihazi, Frank Streit,
Gerrit Erdmann, Simon Kling, Michael Boutros, Claudia Binder and Julia Christina Gross
ABSTRACTS CHAIRS AND SPEAKERS
Junior Group Leader, Extracellular Signaling Lab, Haematol-
ogy and Oncology/University Medical Center Göttingen and
Developmental Biochemistry/Göttingen Center for Molecular
Biosciences (GZMB), Ernst-Caspari-Haus, Justus-von-Liebig
Weg 11, 37077 Göttingen
Extracellular vesicles (EVs) are membrane particles secreted
from cells into all body fluids. Several EV populations exist
differing in size and cellular origin. Using differential centrif-
ugation EVs pelleting at 14,000 g (“microvesicles” (MV)) and
100,000 g (“exosomes”) are distinguishable by protein markers,
yet both carry active Wnt5A on their surface. Neutral sphin-
gomyolinase (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 secretion of MVs is unknown.
Here we investigated how SMPD2/3 impact concentration, size
and composition of 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 shifted onto MVs under these
conditions. Taken together, our data reveal a novel regulato-
ry function of SMPD2/3 in vesicle budding from the plasma
membrane and clearly suggests that – despite the different
vesicle biogenesis – the routes of vesicular export are adapt-
able.competent pore.
Structural basis of gamete fusion
Thomas Krey
Hannover Medical School, Institute of Virology, Structural
Virology Group, Carl-Neuberg-Str. 1, D-30625 Hannover
Sexual reproduction is almost universal in eukaryotic life, and
involves the fusion of male and female haploid gametes into
a diploid cell. The sperm-restricted single-transmembrane
protein HAP2 has been postulated to function in membrane
merger. Its presence in the major eukaryotic taxa – animals,
plants, protists (including important human pathogens like
Plasmodium) - suggests that most eukaryotic organisms share
a common gamete fusion mechanism. We have combined bio-
informatic, biochemical, mutational and structural studies on
the HAP2 from the unicellular alga Chlamydomonas reinhardtii,
revealing homology to class II viral membrane-fusion proteins.
We further show that targeting the segment corresponding to
the fusion loop by mutagenesis or by antibodies blocks gamete
fusion. These results demonstrate that HAP2 is the gamete
fusogen and suggest a mechanism of action akin to viral
fusion, indicating a way to block Plasmodium transmission and
highlighting the impact of virus-cell genetic exchanges on the
evolution of eukaryotic life.
