TY - JOUR
T1 - The CPLANE protein Intu protects kidneys from ischemia-reperfusion injury by targeting STAT1 for degradation
AU - Wang, Shixuan
AU - Liu, Aimin
AU - Wu, Guangyu
AU - Ding, Han Fei
AU - Huang, Shuang
AU - Nahman, Stanley
AU - Dong, Zheng
N1 - Funding Information:
We thank Dr. Haase at Vanderbilt University School of Medicine (Nashville, TN) for providing the PEPCK-Cre mouse line, Drs. Lieberthal and Shwartz at Boston University for providing the BUMPT cell line, Dr. Hopfer at Case Western Reserve University for providing the RPTC cell line. This study was supported in part by grants from the National Natural Science Foundation of China (81430017), the National Institutes of Health (DK058831, DK087843) of USA, and the Department of Veterans Administration of USA (BX000319), Carlos and Marguerite Mason Trust.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Intu is known as a ciliogenesis and planar polarity effector (CPLANE) protein. Although roles for Intu have been reported during embryonic development and in the context of developmental disorders, its function and regulation in adult tissues remain poorly understood. Here we show that ablation of Intu specifically in kidney proximal tubules aggravates renal ischemia-reperfusion injury, and leads to defective post-injury ciliogenesis. We identify signal transducer and activator of transcription 1 (STAT1) as a novel interacting partner of Intu. In vitro, Intu and STAT1 colocalize at the centriole/basal body area, and Intu promotes proteasomal degradation of STAT1. During cell stress, Intu expression preserves cilia length and cell viability, and these actions are antagonized by STAT1 expression. Thus, we propose a role for Intu in protecting cells and tissues after injury by targeting STAT1 for degradation and maintaining primary cilia.
AB - Intu is known as a ciliogenesis and planar polarity effector (CPLANE) protein. Although roles for Intu have been reported during embryonic development and in the context of developmental disorders, its function and regulation in adult tissues remain poorly understood. Here we show that ablation of Intu specifically in kidney proximal tubules aggravates renal ischemia-reperfusion injury, and leads to defective post-injury ciliogenesis. We identify signal transducer and activator of transcription 1 (STAT1) as a novel interacting partner of Intu. In vitro, Intu and STAT1 colocalize at the centriole/basal body area, and Intu promotes proteasomal degradation of STAT1. During cell stress, Intu expression preserves cilia length and cell viability, and these actions are antagonized by STAT1 expression. Thus, we propose a role for Intu in protecting cells and tissues after injury by targeting STAT1 for degradation and maintaining primary cilia.
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U2 - 10.1038/s41467-018-03628-8
DO - 10.1038/s41467-018-03628-8
M3 - Article
C2 - 29581513
AN - SCOPUS:85044515372
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1234
ER -