TY - JOUR
T1 - Cross-talk between miR-471-5p and autophagy component proteins regulates LC3-associated phagocytosis (LAP) of apoptotic germ cells
AU - Panneerdoss, Subbarayalu
AU - Viswanadhapalli, Suryavathi
AU - Abdelfattah, Nourhan
AU - Onyeagucha, Benjamin C.
AU - Timilsina, Santosh
AU - Mohammad, Tabrez A.
AU - Chen, Yidong
AU - Drake, Michael
AU - Vuori, Kristiina
AU - Kumar, T. Rajendra
AU - Rao, Manjeet K.
N1 - Funding Information:
We thank GCCRI Core facility, Dr. Lai and Dawn Garcia for performing the RNA seq. We thank Dr. June Lee, Contraception and Reproductive Health Branch CPR, National Institute for Child Health and Human Development, Bethesda, MD, for providing acyline. We thank Dr. Douglas Green (St. Jude Children’s Research Hospital, Memphis, USA) for critically reading the manuscript. We thank Ms. Gabe Waggoner for editing the manuscript. T.R.K. acknowledges the support from The Makowski Foundation. B.C.O is supported by CPRIT training grant RP140105. Y.C. and M.K.R are supported by NCI P30 grant CA054174. M.K.R. is supported by National Institute of Child Health and Human Development Grant HD078654-01, National Institutes of Health.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-017-00590-9
DO - 10.1038/s41467-017-00590-9
M3 - Article
C2 - 28928467
AN - SCOPUS:85029833111
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 598
ER -