Journal
JOURNAL OF NEUROSCIENCE
Volume 37, Issue 48, Pages 11592-11604Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0893-17.2017
Keywords
autism; mushroom body calyx; PSD; Shank; synaptic function
Categories
Funding
- Ministry of Science and Technology [2014CB942803]
- Strategic Priority Research Program B of the Chinese Academy of Sciences [XDB02020400]
- National Science Foundation of China [31110103907, 31490590, 31300903]
- Deutsche Forschungsgemeinschaft [SFB854-B08]
- National Institutes of Health [MH098114, MH104316, HD087795]
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Human genetic studies support that loss-of-function mutations in the SH3 domain and ankyrin repeat containing family proteins (SHANK1-3), the large synaptic scaffolding proteins enriched at the postsynaptic density of excitatory synapses, are causative for autism spectrum disorder and other neuropsychiatric disorders in humans. To better understand the in vivo functions of Shank and facilitate dissection of neuropathology associated with SHANK mutations in human, we generated multiple mutations in the Shank gene, the only member of the SHANK family in Drosophila melanogaster Both male and female Shank null mutants were fully viable and fertile with no apparent morphological or developmental defects. Expression analysis revealed apparent enrichment of Shank in the neuropils of the CNS. Specifically, Shank coexpressed with another PSD scaffold protein, Homer, in the calyx of mushroom bodies in the brain. Consistent with high expression in mushroom body calyces, Shank mutants show an abnormal calyx structure and reduced olfactory acuity. These morphological and functional phenotypes were fully rescued by pan-neuronal reexpression of Shank, and only partially rescued by presynaptic but no rescue by postsynaptic reexpression of Shank. Our findings thus establish a previously unappreciated presynaptic function of Shank.
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