Type II phosphatidylinositol 4-kinase regulates nerve terminal growth and synaptic vesicle recycling

Abstract

Type II phosphatidylinositol 4-kinase (PI4KII) is thought to be associated with synaptic vesicles (SVs) and to be responsible for the majority of PI4K activity in the nervous system. However, the function of PI4KII at the synapse is unknown. We characterized the synaptic phenotypes of a Drosophila melanogaster PI4KII null mutant. We found increased nerve terminal growth in PI4KII null mutants indicating that PI4KII restrains nerve terminal growth. Evoked neurotransmitter release elicited in response to low frequency stimulation and spontaneous neurotransmitter release were not altered in PI4KII null mutants. However, PI4KII null mutants displayed reduced FM1-43 uptake in response to stimulation by high K⁺ saline, indicating impaired SV endocytosis. PI4KII null mutants did not display any defects in FM1-43 unloading, consistent with normal SV exocytosis. Thus, PI4KII is required for SV endocytosis but dispensable for SV exocytosis. Overall, our data show that PI4KII regulates both nerve terminal growth and SV recycling.

Keywords:

• Presynaptic
• Drosophila
• endocytosis
• phosphoinositides

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by startup funds from the University of Windsor (to JSD) and by NSERC [RGPIN #06582; to JSD], by NSERC and Ontario Graduate scholarships (to JB), and by grants from the Cancer Research Society [#9059 and #11202], NSERC [RGPIN #262166] and CIHR [IG1-115714 and MOP-119483] (to JAB).