Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published July 2015 | Accepted Version
Journal Article Open

The translational regulator Cup controls NMJ presynaptic terminal morphology


During oogenesis and early embryonic development in Drosophila, translation of proteins from maternally deposited mRNAs is tightly controlled. We and others have previously shown that translational regulatory proteins that function during oogenesis also have essential roles in the nervous system. Here we examine the role of Cup in neuromuscular system development. Maternal Cup controls translation of localized mRNAs encoding the Oskar and Nanos proteins and binds to the general translation initiation factor eIF4E. In this paper, we show that zygotic Cup protein is localized to presynaptic terminals at larval neuromuscular junctions (NMJs). cup mutant NMJs have strong phenotypes characterized by the presence of small clustered boutons called satellite boutons. They also exhibit an increase in the frequency of spontaneous glutamate release events (mEPSPs). Reduction of eIF4E expression synergizes with partial loss of Cup expression to produce satellite bouton phenotypes. The presence of satellite boutons is often associated with increases in retrograde bone morphogenetic protein (BMP) signaling, and we show that synaptic BMP signaling is elevated in cup mutants. cup genetically interacts with four genes (EndoA, WASp, Dap160, and Synj) encoding proteins involved in endocytosis that are also neuronal modulators of the BMP pathway. Endophilin protein, encoded by the EndoA gene, is downregulated in a cup mutant. Our results are consistent with a model in which Cup and eIF4E work together to ensure efficient localization and translation of endocytosis proteins in motor neurons and control the strength of the retrograde BMP signal.

Additional Information

© 2015 Published by Elsevier Inc. Received 12 October 2014; Revised 14 June 2015; Accepted 18 June 2015; Available online 20 June 2015. We thank Jim Wilhelm (UC San Diego) for helpful discussions, Craig Smibert (University of Toronto, Toronto, Canada) for the UAS-Cup cDNA, Akira Nakamura (Riken Center for Developmental Biology, Japan), Jim Wilhelm, Allan Spradling (Carnegie Institution for Science, Maryland), Hugo Bellen (Baylor University), the Developmental Studies Hybridoma Bank, and the Drosophila Stock Center for stocks and antibodies. We thank Elena Armand for technical assistance and the Biological Imaging facility (CalTech) for access to Zeiss LSM 510 Confocal. We thank the TRiP at Harvard Medical School (NIH/NIGMS R01-GM084947) for providing transgenic RNAi fly stocks. This work was supported by an NIH RO1 grant to K.Z., NS62821.

Attached Files

Accepted Version - nihms705152.pdf


Files (1.3 MB)
Name Size Download all
1.3 MB Preview Download

Additional details

August 22, 2023
October 23, 2023