Neural-specific overexpression of Drosophila Plenty of SH3s (DPOSH) extends the longevity of adult flies

Extended longevity mutants are extremelyuseful to understand the molecular mechanism oflongevity determination. Here we reportidentification and characterization of the Drosophila Plenty of SH3s (DPOSH) gene,a candidate that might be associated with theextended longevity phenotype. DPOSHencodes a protein containing a RING fingerdomain and four SH3 domains. We showed thatneural-specific overexpression of DPOSHcould extend the mean longevity of adult fliesby 14% at 25 °C without affectingviability or morphology. In contrast, forcedexpression of DPOSH in developingimaginal discs produced various phenotypesincluding lethality and morphological defectssuch as loss of crossvein, notched wing, anddisordered hair polarity. Puckered, atarget gene of JNK/SAPK pathway, was activatedby overexpression of DPOSH and the forcedexpression phenotypes were suppressed byintroducing a mutation of Drosophila JNK(bsk) or JNKK (hep),suggesting that the JNK/SAPK signaling pathwayis one of the critical elements in thedetermination of longevity.