The14-3-3Protein PAR-5and AMPK Homologous Protein AAK-2Regulate Lifespan And Stress Response Signaling In Caenorhabditis Elegans

We used C. elegans in this paper to study the regulatory mechanism of14-3-3protein PAR-5overexpression in the nervous system to extend life span, and the regulation of AMPK protein AAK-2on stress response, in order to further understand the14-3-3and AMPK protein families. Previous studies showed that ftt-2and par-5, two C. elegans genes encoding14-3-3proteins, are widely expressed in many tissues and overexpressing both genes can extend life span, however, overexpressing only par-5but not ftt-2in nervous system can extend lifespan significantly. In present study, analyses of transgenic worms’ life span showed that prolonged life span by overexpressing par-5in nervous system did not depend on lifespan regulator JNK-1expressing in nervous system specifically, but on another important lifespan regulator DAF-16. AMPK protein AAK-2plays an important role in the regulation of stress response, and aak-2mutants are sensitive to a variety of environmental stresses. In order to clarify the regulation mechanism of AAK-2in stress response, we first studied the nucleo-cytoplasmic distribution of AAK-2under heat shock and starvation conditions. We next examined the effect of different AAK-2protein domains on its function. Finally we measured AAK-2protein level under different stress conditions. Our results showed that AAK-2is a key regulator of C. elegans response to heat shock and oxidative stress; AAK-2may not change its nucleo-cytoplasmic distribution to cope with stress; different AAK-2protein domains have different effects on its nucleo-cytoplasmic distribution; and worms might partially up-regulate AAK-2protein level to cope with specific stress conditions, heat shock for example. Given14-3-3and AMPK proteins are highly conserved in evolution, the research work in this paper will help to understand the regulation mechanism of AMPK and14-3-3protein in life span and stress in other species.