RT Journal Article
SR Electronic
T1 SNAP-25 gene family members differentially support secretory vesicle fusion
JF Journal of Cell Science
JO J. Cell Sci.
FD The Company of Biologists Ltd
SP 1877
OP 1889
DO 10.1242/jcs.201889
VO 130
IS 11
A1 Arora, Swati
A1 Saarloos, Ingrid
A1 Kooistra, Robbelien
A1 van de Bospoort, Rhea
A1 Verhage, Matthijs
A1 Toonen, Ruud F.
YR 2017
UL http://jcs.biologists.org/content/130/11/1877.abstract
AB Neuronal dense-core vesicles (DCVs) transport and secrete neuropeptides necessary for development, plasticity and survival, but little is known about their fusion mechanism. We show that Snap-25-null mutant (SNAP-25 KO) neurons, previously shown to degenerate after 4 days in vitro (DIV), contain fewer DCVs and have reduced DCV fusion probability in surviving neurons at DIV14. At DIV3, before degeneration, SNAP-25 KO neurons show normal DCV fusion, but one day later fusion is significantly reduced. To test if other SNAP homologs support DCV fusion, we expressed SNAP-23, SNAP-29 or SNAP-47 in SNAP-25 KO neurons. SNAP-23 and SNAP-29 rescued viability and supported DCV fusion in SNAP-25 KO neurons, but SNAP-23 did so more efficiently. SNAP-23 also rescued synaptic vesicle (SV) fusion while SNAP-29 did not. SNAP-47 failed to rescue viability and did not support DCV or SV fusion. These data demonstrate a developmental switch, in hippocampal neurons between DIV3 and DIV4, where DCV fusion becomes SNAP-25 dependent. Furthermore, SNAP-25 homologs support DCV and SV fusion and neuronal viability to variable extents – SNAP-23 most effectively, SNAP-29 less so and SNAP-47 ineffectively.