Abstract:
:Neurons can maintain stable synaptic connections across adult life. However, the signals that regulate expression of synaptic proteins in the mature brain are incompletely understood. Here, we describe a transcriptional feedback loop between the biosynthesis and repertoire of specific phospholipids and the synaptic vesicle pool in adult Drosophila photoreceptors. Mutations that disrupt biosynthesis of a subset of phospholipids cause degeneration of the axon terminal and loss of synaptic vesicles. Although degeneration of the axon terminal is dependent on neural activity, activation of sterol regulatory element binding protein (SREBP) is both necessary and sufficient to cause synaptic vesicle loss. Our studies demonstrate that SREBP regulates synaptic vesicle levels by interacting with tetraspanins, critical organizers of membranous organelles. SREBP is an evolutionarily conserved regulator of lipid biosynthesis in non-neuronal cells; our studies reveal a surprising role for this feedback loop in maintaining synaptic vesicle pools in the adult brain.
journal_name
Neuronjournal_title
Neuronauthors
Tsai JW,Kostyleva R,Chen PL,Rivas-Serna IM,Clandinin MT,Meinertzhagen IA,Clandinin TRdoi
10.1016/j.neuron.2019.01.015subject
Has Abstractpub_date
2019-02-20 00:00:00pages
721-737.e4issue
4eissn
0896-6273issn
1097-4199pii
S0896-6273(19)30016-9journal_volume
101pub_type
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