Abstract：
:The endoplasmic reticulum (ER) is an extensive organelle in neurons with important roles at synapses including the regulation of cytosolic Ca2+, neurotransmission, lipid metabolism, and membrane trafficking. Despite intriguing evidence for these crucial functions, how the presynaptic ER influences synaptic physiology remains enigmatic. To gain insight into this question, we have generated and characterized mutations in the single extended synaptotagmin (Esyt) ortholog in Drosophila melanogaster Esyts are evolutionarily conserved ER proteins with Ca2+-sensing domains that have recently been shown to orchestrate membrane tethering and lipid exchange between the ER and plasma membrane. We first demonstrate that Esyt localizes to presynaptic ER structures at the neuromuscular junction. Next, we show that synaptic growth, structure, and homeostatic plasticity are surprisingly unperturbed at synapses lacking Esyt expression. However, neurotransmission is reduced in Esyt mutants, consistent with a presynaptic role in promoting neurotransmitter release. Finally, neuronal overexpression of Esyt enhances synaptic growth and the sustainment of the vesicle pool during intense activity, suggesting that increased Esyt levels may modulate the membrane trafficking and/or resting Ca2+ pathways that control synapse extension. Thus, we identify Esyt as a presynaptic ER protein that can promote neurotransmission and synaptic growth, revealing the first in vivo neuronal functions of this conserved gene family.
journal_name
Geneticsjournal_title
Geneticsauthors
Kikuma K,Li X,Kim D,Sutter D,Dickman DKdoi
10.1534/genetics.117.300261subject
Has Abstractpub_date
2017-11-01 00:00:00pages
993-1006issue
3eissn
0016-6731issn
1943-2631pii
genetics.117.300261journal_volume
207pub_type
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