Caenorhabditis elegans Muscleblind homolog mbl-1 functions in neurons to regulate synapse formation.
BACKGROUND
The sequestration of Muscleblind splicing regulators results in myotonic dystrophy. Previous work on Muscleblind has largely focused on its roles in muscle development and maintenance due to the skeletal and cardiac muscle degeneration phenotype observed in individuals with the disorder. However, a number of reported nervous system defects suggest that Muscleblind proteins function in other tissues as well.


RESULTS
We have identified a mutation in the Caenorhabditis elegans homolog of Muscleblind, mbl-1, that is required for proper formation of neuromuscular junction (NMJ) synapses. mbl-1 mutants exhibit selective loss of the most distal NMJ synapses in a C. elegans motorneuron, DA9, visualized using the vesicle-associated protein RAB-3, as well as the active zone proteins SYD-2/liprin-α and UNC-10/Rim. The proximal NMJs appear to have normal pre- and postsynaptic specializations. Surprisingly, expressing a mbl-1 transgene in the presynaptic neuron is sufficient to rescue the synaptic defect, while muscle expression has no effect. Consistent with this result, mbl-1 is also expressed in neurons.


CONCLUSIONS
Based on these results, we conclude that in addition to its functions in muscle, the Muscleblind splice regulators also function in neurons to regulate synapse formation.
Department of Biology, Howard Hughes Medical Institute, Stanford University, 385 Serra Mall, Stanford, California 94305, USA.
Kerri A
KA
Spilker
George J
GJ
Wang
Madina S
MS
Tugizova
Kang
K
Shen
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D008124:Locomotion / Q000235:genetics; D009043:Motor Activity / Q000235:genetics; D009046:Motor Neurons / Q000502:physiology; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D013569:Synapses / Q000235:genetics* / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D016601:RNA-Binding Proteins; C526262:mbl-1 protein, C elegans