We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Fife, a Drosophila Piccolo-RIM Homolog, Promotes Active Zone Organization and Neurotransmitter Release.
- Authors
Bruckner, Joseph J.; Gratz, Scott J.; Slind, Jessica K.; Geske, Richard R.; Cummings, Alexander M.; Galindo, Samantha E.; Donohue, Laura K.; O'Connor-Giles, Kate M.
- Abstract
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 a piccolo-rim-related gene in invertebrates, together with molecular phylogenetic analyses that indicate the encoded proteins may represent Piccolo orthologs. In accordance, we find that the Drosophila homolog, Fife, is neuronal and localizes to presynaptic AZs. To investigate the in vivo function of Fife, we generated a deletion of the fife locus. We find that evoked neurotrans-mitter release is substantially decreased in fife mutants and loss of fife results in motor deficits. Through morphological analysis offife synapses, 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.
- Subjects
DROSOPHILA physiology; NEUROTRANSMITTERS; CYTOSKELETAL proteins; HOMOLOGY (Biology); DROSOPHILA genetics; DELETION mutation; MOLECULAR phylogeny; SYNAPTIC vesicles
- Publication
Journal of Neuroscience, 2012, Vol 32, Issue 48, p1748
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.3267-12.2012