Abstract
The microtubule network is crucial for cell structure and function. Patronin is a conserved protein involved in protecting the minus end of microtubules. Conversely, Klp10A is a kinesin-like microtubule depolymerase. Here we report the role of Drosophila Patronin and Klp10A for cell survival in developing organs. Loss of Patronin reduces the size of organs by activation of a caspase in imaginal discs. Reduced wing by Patronin RNAi is suppressed by knockdown of Spastin (Spas) but not Katanin 60, suggesting that Patronin is inhibitory to the severing function of Spas at the minus end. Patronin RNAi phenotype is also recovered by overexpressing Death-associated inhibitor of apoptosis 1 (Diap1), a Yorkie target gene. Heterozygote mutations in Hippo pathway genes, including hippo and warts (wts), suppress the Patronin RNAi wing phenotypes. Furthermore, Patronin physically interacts with Merlin and Expanded while reducing their function. Patronin and Klp10A antagonistically regulate their levels. Wing phenotypes of Patronin RNAi are rescued by knockdown of Klp10A, consistent with their antagonistic interaction. Klp10A overexpression also causes organ size reduction that is partially suppressed by Diap1 overexpression or wts heterozygote mutation. Taken together, this study suggests that the antagonistic interaction between Patronin and Klp10A is required for controlling cell survival and organ size by modulating microtubule stability and Hippo components.
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12 August 2020
A Correction to this paper has been published: https://doi.org/10.1038/s41418-020-00603-z
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Acknowledgements
We are grateful to all who kindly provided reagents and fly stocks described in “Materials and methods”, especially, N. Tapon, R. Fehon, G. Halder, D. St. Johnston, D. Glover, K. McKim. We also thank K.-O. Cho, M. Takeichi, C. Desplan, and our lab members for their valuable comments. This research was supported by NRF-2014K1A1A2042982 and NRF-2017R1A2B3007516 through the National Research Foundation of Korea, funded by the Korean Ministry of Education, Science & Technology.
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D-WY and K-WC designed the study, and D-WY performed experiments. D-WY and K-WC analyzed the data and wrote the paper.
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Yang, DW., Choi, KW. Suppression of Patronin deficiency by altered Hippo signaling in Drosophila organ development. Cell Death Differ 28, 233–250 (2021). https://doi.org/10.1038/s41418-020-0597-x
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DOI: https://doi.org/10.1038/s41418-020-0597-x
