%0 Journal Article
%T Caenorhabditis elegans Muscleblind homolog mbl-1 functions in neurons to regulate synapse formation
%A Kerri A Spilker
%A George J Wang
%A Madina S Tugizova
%A Kang Shen
%J Neural Development
%D 2012
%I BioMed Central
%R 10.1186/1749-8104-7-7
%X 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-¦Á 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.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.Myotonic dystrophy type 1 (DM1) is a disorder characterized by progressive muscle degeneration and myotonia, or the failure of muscles to relax. The underlying molecular cause of DM1 is an expansion of CTG-repeats in the 3' untranslated region of the gene DMPK (dystrophia myotonica-protein kinase) [1]. These expanded CUG-repeats bind with high affinity to the Muscleblind-like (MBNL) alternative splicing regulators and result in the sequestration of MBNL proteins in the nucleus [2,3], rendering them unable to perform their normal splicing functions and disease phenotypes are due partly to changes in splicing of MBNL target genes (reviewed in [4]).All metazoans have at least one MBNL-type splicing regulator, each with two or four zinc-finger CCCH RNA-binding domains in the amino-terminal half of the protein [5]. In crystal structures, the zinc fingers bind to specific RNA sequences and it is hypothesized that MBNL proteins regulate splicing by binding directly to RNA [6].Because MBNL proteins are enriched in muscle tissue and skeletal and cardiac muscle defects are prominent features of DM1, most studies of MBNL genes have
%U http://www.neuraldevelopment.com/content/7/1/7