Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Department of Genetics and Developmental Biology, Southeast University Medical school, Nanjing 210009, China

Abstract 

Objective
To study the role of HLB-1 in regulating the organization and function of neuromuscular junctions in nematode Caenorhabditis elegans  
Methods 
To evaluate the functions of HLB-1 in regulating the organization and function of neuromuscular junctions, effects of hlb-1 mutation on the synaptic structures were revealed by uncovering the expression patterns of SNB-1::GFP and UNC-49::GFP, and pharmacologic assays with aldicarb and levamisole were also used to test the synaptic functions. Further rescue and mosaic analysis confirmed HLB-1’s role in regulating the organization and function of neuromuscular junctions. 
Results 
Loss of HLB-1 function did not result in defects in neuronal outgrowth or neuronal loss, but caused obvious defects of SNB-1::GFP and UNC-49::GFP puncta localization, suggesting the altered presynaptic and postsynaptic structures. The mutant animals exhibited severe defects in locomotion behaviors and altered responses to an inhibitor of acetylcholinesterase and a cholinergic agonist, indicating the altered presynaptic and postsynaptic functions. Rescue and mosaic analysis experiments suggested that HLB-1 regulated synaptic functions in a cell nonautonomously way. Moreover, HLB-1 expression was not required for the presynaptic active zone morphology. Genetic evidence further demonstrated that hlb-1 acted in a parallel pathway with syd-2 to regulate the synaptic functions. 
Conclusion 
HLB-1 appeared as a new regulator for the organization and function of neuromuscular junctions in C. elegans.

Keywords

HLB-1; synaptic function; neuromuscular junction; SYD-2; Caenorhabditis elegans

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