Ca<sup>2+</sup>-calpains axis regulates Yki stability and activity in Drosophila

Chaojun Zhai; Yunfeng Wang; Shenao Qi; Muhan Yang; Shian Wu

doi:10.1016/j.jgg.2024.04.011

Volume 51 Issue 10

Oct. 2024

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Article Navigation > Journal of Genetics and Genomics > 2024 > 51(10): 1020-1029

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Ca²⁺-calpains axis regulates Yki stability and activity in Drosophila

doi: 10.1016/j.jgg.2024.04.011

The State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, College of Life Sciences, Nankai University, Tianjin 300071, China

Funds:

We also thank Ruming Liu, Li Jiao, and Lingling Wang for technical supports from the Core Facility of Nankai University. This research was funded by the National Natural Science Foundation of China (32170714, 31970733, and 31671513) and the Fundamental Research Funds for the Central Universities, Nankai University (63185024).

Received Date: 2024-01-26
Accepted Date: 2024-04-15
Rev Recd Date: 2024-04-14

Available Online: 2025-06-06

Publish Date: 2024-04-24

Abstract

Abstract

Yorkie (Yki) is a key effector of the Hippo pathway that activates the expression of targets by associating with the transcription factor Scalloped. Various upstream signals, such as cell polarity and mechanical cues, control transcriptional programs by regulating Yki activity. Searching for Yki regulatory factors has far-reaching significance for studying the Hippo pathway in development and human diseases. In this study, we identify Calpain-A (CalpA) and Calpain-B (CalpB), two calcium (Ca²⁺)-dependent modulatory proteases of the calpain family, as critical regulators of Yki in Drosophila that interact with Yki, respectively. Ca²⁺ induces Yki cleavage in a CalpA/CalpB-dependent manner, and the protease activity of CalpA/CalpB is pivotal for the cleavage. Furthermore, overexpression of CalpA or CalpB in Drosophila partially restores the large wing phenotype caused by Yki overexpression, and F98 of Yki is an important cleavage site by the Ca²⁺-calpains axis. Our study uncovers a unique mechanism whereby the Ca²⁺-calpain axis modulates Yki activity through protein cleavage.
- CalpA,
- CalpB,
- Calcium,
- Hippo pathway,
- Yki,
- Drosophila

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References(38)

References

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