A cGMP-dependent protein kinase, encoded by the Drosophila foraging gene, regulates neurotransmission through changes in synaptic structure and function

Abstract

A cGMP-dependent protein kinase (PKG) encoded by the Drosophila foraging (for) gene regulates both synaptic structure (nerve terminal growth) and function (neurotransmission) through independent mechanisms at the Drosophila larval neuromuscular junction (nmj). Glial for is known to restrict nerve terminal growth, whereas presynaptic for inhibits synaptic vesicle (SV) exocytosis during low frequency stimulation. Presynaptic for also facilitates SV endocytosis during high frequency stimulation. for’s effects on neurotransmission can occur independent of any changes in nerve terminal growth. However, it remains unclear if for’s effects on neurotransmission affect nerve terminal growth. Furthermore, it’s possible that for’s effects on synaptic structure contribute to changes in neurotransmission. In the present study, we examined these questions using RNA interference to selectively knockdown for in presynaptic neurons or glia at the Drosophila larval nmj. Consistent with our previous findings, presynaptic knockdown of for impaired SV endocytosis, whereas knockdown of glial for had no effect on SV endocytosis. Surprisingly, we found that knockdown of either presynaptic or glial for increased neurotransmitter release in response to low frequency stimulation. Knockdown of presynaptic for did not affect nerve terminal growth, demonstrating that for’s effects on neurotransmission does not alter nerve terminal growth. In contrast, knockdown of glial for enhanced nerve terminal growth. This enhanced nerve terminal growth was likely the cause of the enhanced neurotransmitter release seen following knockdown of glial for. Overall, we show that for can affect neurotransmitter release by regulating both synaptic structure and function.

Keywords:

• Glia
• exocytosis
• endocytosis
• synaptic transmission
• presynaptic
• neurotransmitter release
• nerve terminal growth
• axon

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by grants from NSERC [RGPIN 3397–11 and RGPIN-2016–06185 to M.B.S. and RGPIN #06582 to J.S.D] and a Heart and Stroke fellowship (J.S.D).