Fife, a Drosophila Piccolo-RIM homolog, promotes active zone organization and neurotransmitter release
| Autor: | Richard R. Geske, Joseph J. Bruckner, Laura K. Donohue, Samantha E. Galindo, Alexander M. Cummings, Scott J. Gratz, Jessica K. Slind, Kate M. O'Connor-Giles |
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| Rok vydání: | 2012 |
| Předmět: |
Synaptic vesicle clustering
Mutant Nerve Tissue Proteins Neurotransmission Biology Synaptic vesicle Synaptic Transmission Article Animals Genetically Modified chemistry.chemical_compound Animals Drosophila Proteins Active zone Cytoskeleton Neurotransmitter Neurons General Neuroscience Neuropeptides Brain Cytoskeletal Proteins chemistry Synapses Drosophila Synaptic Vesicles Neuroscience Drosophila Protein |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 32(48) |
| ISSN: | 1529-2401 |
| Popis: | Neuronal communication depends on the precisely orchestrated release of neurotransmitter at specialized sites called active zones (AZs). A small number of scaffolding and cytoskeletal proteins comprising the cytomatrix of the active zone (CAZ) are thought to organize the architecture and functional properties of AZs. The majority of CAZ proteins are evolutionarily conserved, underscoring the fundamental similarities in neurotransmission at all synapses. However, core CAZ proteins Piccolo and Bassoon have long been believed exclusive to vertebrates, raising intriguing questions about the conservation of the molecular mechanisms that regulate presynaptic properties. Here, we present the identification of apiccolo-rim-related gene in invertebrates, together with molecular phylogenetic analyses that indicate the encoded proteins may represent Piccolo orthologs. In accordance, we find that theDrosophilahomolog, Fife, is neuronal and localizes to presynaptic AZs. To investigate thein vivofunction of Fife, we generated a deletion of thefifelocus. We find that evoked neurotransmitter release is substantially decreased infifemutants and loss offiferesults in motor deficits. Through morphological analysis offifesynapses, we identify underlying AZ abnormalities including pervasive presynaptic membrane detachments and reduced synaptic vesicle clustering. Our data demonstrate the conservation of a Piccolo-related protein in invertebrates and identify critical roles for Fife in regulating AZ structure and function. These findings suggest the CAZ is more conserved than previously thought, and open the door to a more complete understanding of how CAZ proteins regulate presynaptic structure and function through genetic studies in simpler model systems. |
| Databáze: | OpenAIRE |
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