Developmental biology, 2021-01, Vol.469, p.37-45
2021
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- Autor(en) / Beteiligte
- Titel
- Syd/JIP3 controls tissue size by regulating Diap1 protein turnover downstream of Yorkie/YAP
- Ist Teil von
- Developmental biology, 2021-01, Vol.469, p.37-45
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2021
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- How organisms control organ size is not fully understood. We found that Syd/JIP3 is required for proper wing size in Drosophila. JIP3 mutations are associated with organ size defects in mammals. The underlying mechanisms are not well understood. We discovered that Syd/JIP3 inhibition results in a downregulation of the inhibitor of apoptosis protein 1 (Diap1) in the Drosophila wing. Correspondingly, Syd/JIP3 deficient tissues exhibit ectopic cell death and yield smaller wings. Syd/JIP3 inhibition generated similar effects in mammalian cells, indicating a conserved mechanism. We found that Yorkie/YAP stimulates Syd/JIP3 in Drosophila and mammalian cells. Notably, Syd/JIP3 is required for the full effect of Yorkie-mediated tissue growth. Thus Syd/JIP3 regulation of Diap1 functions downstream of Yorkie/YAP to control growth. This study provides mechanistic insights into the recent and perplexing link between JIP3 mutations and organ size defects in mammals, including in humans where de novo JIP3 variants are associated with microcephaly. •Syd/JIP3 is required for proper Drosophila wing size.•Syd/JIP3 stabilizes Diap1 to inhibit cell death in Drosophila and in mammalian cells.•Activation of Yorkie/YAP stimulates Syd/JIP3.•Yorkie-mediated tissue growth is highly sensitive to Syd/JIP3 dosage.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0012-1606, 1095-564XeISSN: 1095-564XDOI: 10.1016/j.ydbio.2020.09.017Titel-ID: cdi_proquest_miscellaneous_2449177582
- Format
- –
- Schlagworte
- Animals, Carrier Proteins - genetics, Carrier Proteins - physiology, DIAP1, Drosophila - anatomy & histology, Drosophila - growth & development, Drosophila - metabolism, Drosophila Proteins - genetics, Drosophila Proteins - metabolism, Drosophila Proteins - physiology, Female, Gene Knockdown Techniques, HEK293 Cells, Hippo, Humans, IAP, Inhibitor of Apoptosis Proteins - metabolism, Intracellular Signaling Peptides and Proteins - metabolism, JIP3, MAPK8IP3, Membrane Proteins - genetics, Membrane Proteins - physiology, Mitogen-Activated Protein Kinase Kinases - metabolism, Nuclear Proteins - metabolism, Organ Size, Organ size control, Protein-Serine-Threonine Kinases - metabolism, Trans-Activators - metabolism, Wings, Animal - anatomy & histology, Wings, Animal - growth & development, Yorkie/YAP