title: Functional and direct interaction between the RNA binding protein HuD and active Akt1.
abstract: The RNA binding protein HuD plays essential roles in neuronal development and plasticity. We have previously shown that HuD stimulates translation. Key for this enhancer function is the linker region and the poly(A) binding domain of HuD that are also critical for its function in neurite outgrowth. Here, we further explored the underlying molecular interactions and found that HuD but not the ubiquitously expressed HuR interacts directly with active Akt1. We identify that the linker region of HuD is required for this interaction. We also show by using chimeric mutants of HuD and HuR, which contain the reciprocal linker between RNA-binding domain 2 (RBD2) and RBD3, respectively, and by overexpressing a dominant negative mutant of Akt1 that the HuD-Akt1 interaction is functionally important, as it is required for the induction of neurite outgrowth in PC12 cells. These results suggest the model whereby RNA-bound HuD functions as an adapter to recruit Akt1 to trigger neurite outgrowth. These data might also help to explain how HuD enhances translation of mRNAs that encode proteins involved in neuronal development.
authors.affiliation: Laboratory of Disease Biology, Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan. tosinobu@bikaken.or.jp
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Akira
authors.initials: A
authors.lastname: Fukao
authors.forename: Yumi
authors.initials: Y
authors.lastname: Sasano
authors.forename: Hidenori
authors.initials: H
authors.lastname: Matsuzaki
authors.forename: Ushio
authors.initials: U
authors.lastname: Kikkawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Imataka
authors.forename: Kunio
authors.initials: K
authors.lastname: Inoue
authors.forename: Shogo
authors.initials: S
authors.lastname: Endo
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
authors.forename: Christian
authors.initials: C
authors.lastname: Thoma
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakamoto
mesh_terms: D000818:Animals; D051959:ELAV Proteins / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016501:Neurites / Q000201:enzymology; D016716:PC12 Cells; D054730:Protein Interaction Domains and Motifs; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats
chemical_list: D051959:ELAV Proteins; D051057:Proto-Oncogene Proteins c-akt
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