A non-cell-autonomous role of BEC-1/BECN1/Beclin1 in coordinating cell-cycle progression and stem cell proliferation during germline development
K Ames, DS Da Cunha, B Gonzalez, M Konta, F Lin… - Current Biology, 2017 - cell.com
K Ames, DS Da Cunha, B Gonzalez, M Konta, F Lin, G Shechter, L Starikov, S Wong…
Current Biology, 2017•cell.comThe decision of stem cells to proliferate and differentiate is finely controlled. The
Caenorhabditis elegans germline provides a tractable system for studying the mechanisms
that control stem cell proliferation and homeostasis [1–4]. Autophagy is a conserved cellular
recycling process crucial for cellular homeostasis in many different contexts [5], but its
function in germline stem cell proliferation remains poorly understood. Here, we describe a
function for autophagy in germline stem cell proliferation. We found that autophagy genes …
Caenorhabditis elegans germline provides a tractable system for studying the mechanisms
that control stem cell proliferation and homeostasis [1–4]. Autophagy is a conserved cellular
recycling process crucial for cellular homeostasis in many different contexts [5], but its
function in germline stem cell proliferation remains poorly understood. Here, we describe a
function for autophagy in germline stem cell proliferation. We found that autophagy genes …
Summary
The decision of stem cells to proliferate and differentiate is finely controlled. The Caenorhabditis elegans germline provides a tractable system for studying the mechanisms that control stem cell proliferation and homeostasis [1–4]. Autophagy is a conserved cellular recycling process crucial for cellular homeostasis in many different contexts [5], but its function in germline stem cell proliferation remains poorly understood. Here, we describe a function for autophagy in germline stem cell proliferation. We found that autophagy genes such as bec-1/BECN1/Beclin1, atg-16.2/ATG16L, atg-18/WIPI1/2, and atg-7/ATG7 are required for the late larval expansion of germline stem cell progenitors in the C. elegans gonad. We further show that BEC-1/BECN1/Beclin1 acts independently of the GLP-1/Notch or DAF-7/TGF-β pathways but together with the DAF-2/insulin IGF-1 receptor (IIR) signaling pathway to promote germline stem cell proliferation. Similar to DAF-2/IIR, BEC-1/BECN1/Beclin1, ATG-18/WIPI1/2, and ATG-16.2/ATG16L all promote cell-cycle progression and are negatively regulated by the phosphatase and tensin homolog DAF-18/PTEN. However, whereas BEC-1/BECN1/Beclin1 acts through the transcriptional regulator SKN-1/Nrf1, ATG-18/WIPI1/2 and ATG-16.2/ATG16L exert their function through the DAF-16/FOXO transcription factor. In contrast, ATG-7 functions in concert with the DAF-7/TGF-β pathway to promote germline proliferation and is not required for cell-cycle progression. Finally, we report that BEC-1/BECN1/Beclin1 functions non-cell-autonomously to facilitate cell-cycle progression and stem cell proliferation. Our findings demonstrate a novel non-autonomous role for BEC-1/BECN1/Beclin1 in the control of stem cell proliferation and cell-cycle progression, which may have implications for the understanding and development of therapies against malignant cell growth in the future.
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