RT Journal Article
SR Electronic
T1 Syd/JIP3 Controls Tissue Size by Regulating Diap1 Protein Turnover Downstream of Yorkie/YAP
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.19.049023
DO 10.1101/2020.04.19.049023
A1 Vakil Ahmad
A1 Gangadhar P. Vadla
A1 Chiswili Y. Chabu
YR 2020
UL http://biorxiv.org/content/early/2020/09/06/2020.04.19.049023.abstract
AB 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 protein1 (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.HighlightsSyd/JIP3 is required for proper Drosophila wing sizeSyd/JIP3 stabilizes Diap1 to inhibit cell death in Drosophila and in mammalian cellsActivation of Yorkie/YAP stimulates Syd/JIP3Yorkie-mediated tissue growth is highly sensitive to Syd/JIP3 dosageCompeting Interest StatementThe authors have declared no competing interest.