Contribution of Orb2A Stability in Regulated Amyloid-Like Oligomerization of Drosophila Orb2

How learned experiences persist as memory for a long time is an important question. in drosophila the persistence of memory is dependent upon amyloid-like oligomers of the orb2 protein. however,it is not clear how the conversion of orb2 to the amyloid-like oligomeric state is regulated. the orb2 has two protein isoforms,and the rare orb2a isoform is critical for oligomerization of the ubiquitous orb2b isoform. here,we report the discovery of a protein network comprised of protein phosphatase 2a (pp2a),transducer of erb-b2 (tob),and lim kinase (limk) that controls the abundance of orb2a. pp2a maintains orb2a in an unphosphorylated and unstable state,whereas tob-limk phosphorylates and stabilizes orb2a. mutation of limk abolishes activity-dependent orb2 oligomerization in the adult brain. moreover,tob-orb2 association is modulated by neuronal activity and tob activity in the mushroom body is required for stable memory formation. these observations suggest that the interplay between pp2a and tob-limk activity may dynamically regulate orb2 amyloid-like oligomer formation and the stabilization of memories. © 2014 white-grindley et al.