Differential functions of phosphatidylinositol 4-kinases in neurotransmission and synaptic development

被引:1
作者
Gorey, Claire L. Richter [1 ]
St. Louis, Alexandria P. [1 ]
Chorna, Tetyana [2 ]
Brill, Julie A. [2 ,3 ,4 ]
Dason, Jeffrey S. [1 ]
机构
[1] Univ Windsor, Dept Biomed Sci, Windsor, ON N9B 3P4, Canada
[2] Hosp Sick Children, Cell Biol Program, Toronto, ON, Canada
[3] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada
[4] Univ Toronto, Inst Med Sci, Toronto, ON, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
Drosophila; lipids; phosphatidylinositol; 4-kinases; phosphoinositides; PI4P; presynaptic; PLASMA-MEMBRANE; PROTEIN; CLATHRIN; PI4KIII-ALPHA; ALPHA; INACTIVATION; ENDOCYTOSIS; EXPRESSION; TERMINALS; INTEGRITY;
D O I
10.1111/ejn.16526
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Phosphoinositides, such as PI(4,5)P2, are known to function as structural components of membranes, signalling molecules, markers of membrane identity, mediators of protein recruitment and regulators of neurotransmission and synaptic development. Phosphatidylinositol 4-kinases (PI4Ks) synthesize PI4P, which are precursors for PI(4,5)P2, but may also have independent functions. The roles of PI4Ks in neurotransmission and synaptic development have not been studied in detail. Previous studies on PI4KII and PI4KIII beta at the Drosophila larval neuromuscular junction have suggested that PI4KII and PI4KIII beta enzymes may serve redundant roles, where single PI4K mutants yielded mild or no synaptic phenotypes. However, the precise synaptic functions (neurotransmission and synaptic growth) of these PI4Ks have not been thoroughly studied. Here, we used PI4KII and PI4KIII beta null mutants and presynaptic-specific knockdowns of these PI4Ks to investigate their roles in neurotransmission and synaptic growth. We found that PI4KII and PI4KIII beta appear to have non-overlapping functions. Specifically, glial PI4KII functions to restrain synaptic growth, whereas presynaptic PI4KIII beta promotes synaptic growth. Furthermore, loss of PI4KIII beta or presynaptic PI4KII impairs neurotransmission. The data presented in this study uncover new roles for PI4K enzymes in neurotransmission and synaptic growth. image
引用
收藏
页码:5966 / 5979
页数:14
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