The C2H2 zinc-finger protein SYD-9 is a putative posttranscriptional regulator for synaptic transmission.
Communication between neurons is largely achieved through chemical synapses, where neurotransmitters are released from synaptic vesicles at presynaptic terminals to activate postsynaptic cells. Exo- and endocytosis are coordinated to replenish the synaptic vesicle pool for sustained neuronal activity. We identified syd-9 (syd, synapse defective), a gene that encodes multiple C2H2 zinc-finger domain-containing proteins specifically required for synaptic function in Caenorhabditis elegans. syd-9 loss-of-function mutants exhibit locomotory defects, a diffuse distribution of synaptic proteins, and decreased synaptic transmission with unaffected neurodevelopment. syd-9 mutants share phenotypic and ultrastructural characteristics with mutants that lack synaptic proteins that are required for endocytosis. syd-9 mutants also display genetic interactions with these endocytotic mutants, suggesting that SYD-9 regulates endocytosis. SYD-9 proteins are enriched in the nuclei of both neuron and muscle cells, but their neuronal expression plays a major role in locomotion. SYD-9 isoforms display a speckle-like expression pattern that is typical of RNA-binding proteins that regulate premRNA splicing. Furthermore, syd-9 functions in parallel with unc-75 (unc, uncoordinated), the C. elegans homologue of the CELF/BrunoL family protein that regulates mRNA alternative splicing and processing, and is also required specifically for synaptic transmission. We propose that neuronal SYD-9 proteins are previously uncharacterized and specific posttranscriptional regulators of synaptic vesicle endocytosis.
Wang
Ying
Y
*Department of Microbiology and Medical Genetics, University of Toronto and The Samuel Lunenfeld Research Institute, Toronto, ON, Canada M5G 1X5.
Gracheva
Elena O
EO
Department of Biological Sciences, University of Illinois, Chicago, IL 60607; and.
Richmond
Janet
J
Department of Biological Sciences, University of Illinois, Chicago, IL 60607; and.
Kawano
Taizo
T
*Department of Microbiology and Medical Genetics, University of Toronto and The Samuel Lunenfeld Research Institute, Toronto, ON, Canada M5G 1X5.
Couto
Jillian M
JM
*Department of Microbiology and Medical Genetics, University of Toronto and The Samuel Lunenfeld Research Institute, Toronto, ON, Canada M5G 1X5.
Calarco
John A
JA
*Department of Microbiology and Medical Genetics, University of Toronto and The Samuel Lunenfeld Research Institute, Toronto, ON, Canada M5G 1X5.
Vijayaratnam
Vijhee
V
*Department of Microbiology and Medical Genetics, University of Toronto and The Samuel Lunenfeld Research Institute, Toronto, ON, Canada M5G 1X5.
Jin
Yishi
Y
Department of Molecular Cell and Developmental Biology and Howard Hughes Medical Institute, University of California, Santa Cruz, CA 95064.
Zhen
Mei
M
*Department of Microbiology and Medical Genetics, University of Toronto and The Samuel Lunenfeld Research Institute, Toronto, ON, Canada M5G 1X5; zhen@mshri.on.ca.
D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D048430:Cell Shape; D004705:Endocytosis / Q000235:genetics; D005786:Gene Expression Regulation; D008854:Microscopy, Electron; D032342:Muscle Cells / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D016335:Zinc Fingers
D029742:Caenorhabditis elegans Proteins; D020033:Protein Isoforms; C512462:SYD-9 protein, C elegans; D014157:Transcription Factors