RRC ID 57358
著者 Huang J, Wang H.
タイトル Hsp83/Hsp90 Physically Associates with Insulin Receptor to Promote Neural Stem Cell Reactivation.
ジャーナル Stem Cell Reports
Abstract Neural stem cells (NSCs) have the ability to exit quiescence and reactivate in response to physiological stimuli. In the Drosophila brain, insulin receptor (InR)/phosphatidylinositol 3-kinase (PI3K)/Akt pathway triggers NSC reactivation. However, intrinsic mechanisms that control the InR/PI3K/Akt pathway during reactivation remain unknown. Here, we have identified heat shock protein 83 (Hsp83/Hsp90), a molecular chaperone, as an intrinsic regulator of NSC reactivation. Hsp83 is both necessary and sufficient for NSC reactivation by promoting the activation of InR pathway in larval brains in the presence of dietary amino acids. Both Hsp83 and its co-chaperone Cdc37 physically associate with InR. Finally, reactivation defects observed in brains depleted of hsp83 were rescued by over-activation of the InR/PI3K/Akt pathway, suggesting that Hsp83 functions upstream of the InR/PI3K/Akt pathway during NSC reactivation. Given the conservation of Hsp83 and the InR pathway, our finding may provide insights into the molecular mechanisms underlying mammalian NSC reactivation.
巻・号 11(4)
ページ 883-896
公開日 2018-10-9
DOI 10.1016/j.stemcr.2018.08.014
PII S2213-6711(18)30358-8
PMID 30245208
PMC PMC6178561
MeSH Amino Acids / metabolism Animals Cell Cycle Proteins / metabolism Down-Regulation Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / metabolism* Heat-Shock Proteins / genetics Heat-Shock Proteins / metabolism* Molecular Chaperones / metabolism Neural Stem Cells / cytology* Neural Stem Cells / metabolism* Phosphatidylinositol 3-Kinases / metabolism Phosphorylation Protein Binding Proto-Oncogene Proteins c-akt / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Receptor Protein-Tyrosine Kinases / metabolism* Signal Transduction
IF 5.499
引用数 4
リソース情報
ショウジョウバエ DGRC#111379