title: Contribution of Orb2A stability in regulated amyloid-like oligomerization of Drosophila Orb2.
abstract: 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.
authors: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.
authors: Erica
authors: E
authors: White-Grindley
authors: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
authors: Liying
authors: L
authors: Li
authors: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
authors: Repon
authors: R
authors: Mohammad Khan
authors: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.
authors: Fengzhen
authors: F
authors: Ren
authors: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.
authors: Anita
authors: A
authors: Saraf
authors: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.
authors: Laurence
authors: L
authors: Florens
authors: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America ; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
authors: Kausik
authors: K
authors: Si
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D054461:Lim Kinases / Q000378:metabolism; D057567:Memory, Long-Term; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D060066:Protein Interaction Maps; D020033:Protein Isoforms / Q000378:metabolism; D055503:Protein Multimerization; D054648:Protein Phosphatase 2 / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D014157:Transcription Factors / Q000378:metabolism*; D014439:Tyramine / Q000502:physiology; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism*
chemical_list: D000682:Amyloid; D029721:Drosophila Proteins; C529066:Orb2 protein, Drosophila; D020033:Protein Isoforms; C000592243:Tob protein, Drosophila; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors; D054461:Lim Kinases; D054648:Protein Phosphatase 2; D014439:Tyramine