Distinct functions of a CNS/PNS-dependent protein kinase in nerve terminal growth and synaptic vesicle cycling

Document Type

Article

Publication Title

Journal of Cell Science

Publication Date

4-1-2019

Volume

132

Issue

7

Keywords

Endocytosis, Exocytosis, Neurotransmitter release, Presynaptic, Synaptic transmission

DOI

10.1242/jcs.227165

ISSN

00219533

Abstract

Sustained neurotransmission requires the tight coupling of synaptic vesicle (SV) exocytosis and endocytosis. The mechanisms underlying this coupling are poorly understood. We tested the hypothesis that a CNS/PNS-dependent protein kinase (PKG), encoded by the foraging (for) gene in Drosophila melanogaster, is critical for this process using a for null mutant, genomic rescues and tissue-specific rescues. We uncoupled the exocytic and endocytic functions of FOR in neurotransmission using a temperature-sensitive shibire mutant in conjunction with fluorescein-assisted light inactivation of FOR. We discovered a dual role for presynaptic FOR, in which FOR inhibits SV exocytosis during low-frequency stimulation by negatively regulating presynaptic Ca2+ levels and maintains neurotransmission during highfrequency stimulation by facilitating SV endocytosis. Additionally, glial FOR negatively regulated nerve terminal growth through TGF-β signalling, and this developmental effect was independent of the effects of FOR on neurotransmission. Overall, FOR plays a critical role in coupling SV exocytosis and endocytosis, thereby balancing these two components to maintain sustained neurotransmission.

E-ISSN

14779137

PubMed ID

30837290

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