Cross-talk between miR-471-5p and autophagy component proteins regulates LC3-associated phagocytosis (LAP) of apoptotic germ cells

Subbarayalu Panneerdoss, Suryavathi Viswanadhapalli, Nourhan Abdelfattah, Benjamin C. Onyeagucha, Santosh Timilsina, Tabrez A. Mohammad, Yidong Chen, Michael Drake, Kristiina Vuori, T. Rajendra Kumar and Manjeet K. Rao ()
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Subbarayalu Panneerdoss: University of Texas Health Science Center at San Antonio
Suryavathi Viswanadhapalli: University of Texas Health Science Center at San Antonio
Nourhan Abdelfattah: University of Texas Health Science Center at San Antonio
Benjamin C. Onyeagucha: University of Texas Health Science Center at San Antonio
Santosh Timilsina: University of Texas Health Science Center at San Antonio
Tabrez A. Mohammad: University of Texas Health Science Center at San Antonio
Yidong Chen: University of Texas Health Science Center at San Antonio
Michael Drake: University of Texas Health Science Center at San Antonio
Kristiina Vuori: Sanford-Burnham Medical Research Institute
T. Rajendra Kumar: University of Colorado Denver
Manjeet K. Rao: University of Texas Health Science Center at San Antonio

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract Phagocytic clearance of apoptotic germ cells by Sertoli cells is vital for germ cell development and differentiation. Here, using a tissue-specific miRNA transgenic mouse model, we show that interaction between miR-471-5p and autophagy member proteins regulates clearance of apoptotic germ cells via LC3-associated phagocytosis (LAP). Transgenic mice expressing miR-471-5p in Sertoli cells show increased germ cell apoptosis and compromised male fertility. Those effects are due to defective engulfment and impaired LAP-mediated clearance of apoptotic germ cells as miR-471-5p transgenic mice show lower levels of Dock180, LC3, Atg12, Becn1, Rab5 and Rubicon in Sertoli cells. Our results reveal that Dock180 interacts with autophagy member proteins to constitute a functional LC3-dependent phagocytic complex. We find that androgen regulates Sertoli cell phagocytosis by controlling expression of miR-471-5p and its target proteins. These findings suggest that recruitment of autophagy machinery is essential for efficient clearance of apoptotic germ cells by Sertoli cells using LAP.

Date: 2017
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DOI: 10.1038/s41467-017-00590-9

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