Sphingolipids Regulate Neuromuscular Synapse Structure and function in Drosophila

Ryan John Hatcher West, Laura Briggs, Maria Perona Fjeldstad, Richard R. Ribchester, Sean Sweeney

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Sphingolipids are found in abundance at synapses and have been implicated in
regulation of synapse structure, function and degeneration. Their precise role in
these processes, however, remains obscure. Serine Palmitoyl-transferase (SPT)
is the first enzymatic step for synthesis of sphingolipids. Analysis of the
Drosophila larval neuromuscular junction revealed mutations in the SPT enzyme
subunit, lace/SPTLC2 resulted in deficits in synaptic structure and function.
Although neuromuscular junction (NMJ) length is normal in lace mutants, the
number of boutons per NMJ is reduced to ~50% of the wild type number.
Synaptic boutons in lace mutants are much larger but show little perturbation to
the general ultrastructure. Electrophysiological analysis of lace mutant synapses
revealed strong synaptic transmission coupled with predominance of depression
over facilitation. The structural and functional phenotypes of lace mirrored
aspects of Basigin (Bsg), a small Ig-domain adhesion molecule also known to
regulate synaptic structure and function. Mutant combinations of lace and Bsg
generated large synaptic boutons, while lace mutants showed abnormal
accumulation of Bsg at synapses, suggesting that Bsg requires sphingolipid to
regulate structure of the synapse. In support of this, we found Bsg to be enriched in lipid rafts. Our data points to a role for sphingolipids in the regulation and fine-tuning of synaptic structure and function while sphingolipid regulation of synaptic structure may be mediated via the activity of Bsg.
Original languageEnglish
JournalJournal of comparative neurology
Early online date15 May 2018
Publication statusPublished - 1 Sept 2018

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