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The Rheb-mTORC1 Coordinates Cell Cycle Progression and Endoreplication in Bombyx mori
Zhangchen Tang1,2, Huawei Liu1,2, Qingsong Liu1,2
1Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, Biological Science Research Center, Southwest University, Chongqing 400715, China.
Abstract:
The mechanistic target of the Rapamycin complex 1 (mTORC1) signaling pathway plays a pivotal role in regulating crucial life processes, including cell growth and proliferation, by sensing and integrating various signals, such as growth factors, energy status, and amino acids. Our previous studies showed that activation of the mTORC1 signaling pathway enhances silk protein synthesis and silk gland size. Here, the potential of the molecular mechanism mTORC1 to regulate the growth and development of silk gland cells was investigated. Inhibiting mTORC1 with rapamycin decreased proliferation in the Bombyx mori embryonic (BmE) cells and endoreplication in silk gland cells, reducing CyclinB and CyclinE protein levels and DNA content, and arresting the BmE cell cycle at G2/M. Conversely, the overexpression of Ras homolog enriched in brain (Rheb) led to increased proliferation of BmE cells and endoreplication in silk gland cells, as well as a significant elevation in DNA content. This study provides a molecular explanation for the increase in silk protein synthesis and silk gland length through the activation of mTORC1, thereby refining the regulatory network of the silkworm endoreplication and providing new molecular targets for breeding high-yield varieties of Bombyx mori.
Insights
The mechanistic target of the Rapamycin complex 1 (mTORC1) pathway regulates silk gland cell growth. Inhibiting mTORC1 reduces cell proliferation and DNA content, while Rheb overexpression enhances these processes in Bombyx mori.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The mechanistic target of the Rapamycin complex 1 (mTORC1) signaling pathway is crucial for cell growth and proliferation.
- Previous studies indicated mTORC1 activation enhances silk protein synthesis and silk gland size in Bombyx mori.
- Understanding mTORC1's role in silk gland development is key to improving silkworm yields.
Purpose of the Study:
- To investigate the molecular mechanism by which mTORC1 regulates silk gland cell growth and development.
- To elucidate the role of mTORC1 in controlling cell proliferation and endoreplication in Bombyx mori.
- To identify molecular targets for enhancing silk production in silkworms.
Main Methods:
- Utilized rapamycin to inhibit mTORC1 activity in Bombyx mori embryonic (BmE) cells and silk gland cells.
- Overexpressed Ras homolog enriched in brain (Rheb) to activate the mTORC1 pathway.
- Assessed cell proliferation, endoreplication, cell cycle progression (CyclinB, CyclinE levels), and DNA content.
Main Results:
- mTORC1 inhibition with rapamycin decreased BmE cell proliferation and silk gland cell endoreplication.
- Inhibition led to reduced CyclinB and CyclinE protein levels and DNA content, arresting the cell cycle at G2/M.
- Rheb overexpression significantly increased BmE cell proliferation and silk gland cell endoreplication, elevating DNA content.
Conclusions:
- mTORC1 activation is essential for promoting silk gland cell proliferation and endoreplication in Bombyx mori.
- This study clarifies the molecular basis for mTORC1's positive effect on silk protein synthesis and gland length.
- Findings provide novel molecular targets for breeding high-yield Bombyx mori varieties.
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