TY - JOUR
T1 - Gilgamesh (Gish)/CK1γ regulates tissue homeostasis and aging in adult drosophila midgut
AU - Li, Shuangxi
AU - Tian, Aiguo
AU - Li, Shuang
AU - Han, Yuhong
AU - Wang, Bing
AU - Jiang, Jin
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (GM118063) and Welch Foundation (I-1603) to J. Jiang. J. Jiang is a Eugene McDermott Endowed Scholar in Biomedical Science at the University of Texas Southwestern.
Funding Information:
This work was supported by grants from the National Institutes of Health (GM118063) and Welch Foundation (I-1603) to J. Jiang. J. Jiang is a Eugene McDermott Endowed Scholar in Biomedical Science at the University of Texas Southwestern. The authors declare no competing financial interests.
Publisher Copyright:
© 2020 Li et al.
PY - 2020
Y1 - 2020
N2 - Adult tissues and organs rely on resident stem cells to generate new cells that replenish damaged cells. To maintain homeostasis, stem cell activity needs to be tightly controlled throughout the adult life. Here, we show that the membrane-associated kinase Gilgamesh (Gish)/CK1γ maintains Drosophila adult midgut homeostasis by restricting JNK pathway activity and that Gish is essential for intestinal stem cell (ISC) maintenance under stress conditions. Inactivation of Gish resulted in aberrant JNK pathway activation and excessive production of multiple cytokines and growth factors that drive ISC overproliferation. Mechanistically, Gish restricts JNK activation by phosphorylating and destabilizing a small GTPase, Rho1. Interestingly, we find that Gish expression is down-regulated in aging guts and that increasing Gish activity in aging guts can restore tissue homeostasis. Hence, our study identifies Gish/CK1γ as a novel regulator of Rho1 and gatekeeper of tissue homeostasis whose activity is compromised in aging guts.
AB - Adult tissues and organs rely on resident stem cells to generate new cells that replenish damaged cells. To maintain homeostasis, stem cell activity needs to be tightly controlled throughout the adult life. Here, we show that the membrane-associated kinase Gilgamesh (Gish)/CK1γ maintains Drosophila adult midgut homeostasis by restricting JNK pathway activity and that Gish is essential for intestinal stem cell (ISC) maintenance under stress conditions. Inactivation of Gish resulted in aberrant JNK pathway activation and excessive production of multiple cytokines and growth factors that drive ISC overproliferation. Mechanistically, Gish restricts JNK activation by phosphorylating and destabilizing a small GTPase, Rho1. Interestingly, we find that Gish expression is down-regulated in aging guts and that increasing Gish activity in aging guts can restore tissue homeostasis. Hence, our study identifies Gish/CK1γ as a novel regulator of Rho1 and gatekeeper of tissue homeostasis whose activity is compromised in aging guts.
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U2 - 10.1083/JCB.201909103
DO - 10.1083/JCB.201909103
M3 - Article
C2 - 32328627
AN - SCOPUS:85084030969
SN - 0021-9525
VL - 219
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
M1 - e201909103
ER -