HLB-1 functions as a new regulator for the organization and function of neuromuscular junctions in nematode Caenorhabditis elegans.
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.


CONCLUSIONS
HLB-1 appeared as a new regulator for the organization and function of neuromuscular junctions in C. elegans.
Wang
Da-Yong
DY
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. dayongw@seu.edu.cn
Wang
Yang
Y
D000367:Age Factors; D020816:Amino Acid Motifs / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000502:physiology; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D008124:Locomotion / Q000235:genetics; D009154:Mutation / Q000502:physiology*; D009469:Neuromuscular Junction / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D036341:Intercellular Signaling Peptides and Proteins; D010750:Phosphoproteins; C490598:SYD-2 protein, C elegans; C437625:unc-10 protein, C elegans; D049452:Green Fluorescent Proteins