Behavioral and Synaptic Plasticity Are Impaired upon Lack of the Synaptic Protein SAP47.

The synapse-associated protein of 47kDa(SAP47) is a member of a phylogenetically conserved gene family of hitherto unknown function. In Drosophila, SAP47 is encoded by a single gene (Sap47) and is expressed throughout all synaptic regions of the wild-type larval brain; specifically, electron microscopy reveals anti-SAP47 immunogold labeling within 30 nm of presynaptic vesicles. To analyze SAP47 function, we used the viable and fertile deletion mutant Sap47¹⁵⁶, which suffers from a 1.7 kb deletion in the regulatory region and the first exon. SAP47 cannot be detected by either immunoblotting or immunohistochemistry in Sap47¹⁵⁶ mutants. These mutants exhibit normal sensory detection of odorants and tastants as well as normal motor performance and basic neurotransmission at the neuromuscular junction. However, short-term plasticity at this synapse is distorted. Interestingly, Sap47¹⁵⁶ mutant larvae also show a 50% reduction in odorant-tastant associative learning ability; a similar associative impairment is observed in a second deletion allele (Sap47²⁰¹) and upon reduction of SAP47 levels using RNA interference. In turn, transgenically restoring SAP47 in Sap47¹⁵⁶ mutant larvae rescues the defect in associative function. This report thus is the first to suggest a function for SAP47. It specifically argues that SAP47 is required for proper behavioral and synaptic plasticity in flies-and prompts the question whether its homologs are required for proper behavioral and synaptic plasticity in other species as well. [ABSTRACT FROM AUTHOR]