A Feedforward Loop Between JAK/STAT Downstream Target P115 and STAT in Germline Stem Cells

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2023 Sep 8

PMID 37683644

Authors

Ruiyan Kong

Juan Li

Fuli Liu

Yankun Ma

Hang Zhao

Hanfei Zhao

Meifang Ma

Zhouhua Li

Affiliations

Soon will be listed here.

Abstract

The maintenance of germline stem cells (GSCs) is essential for tissue homeostasis. JAK/STAT signaling maintains GSC fate in Drosophila testis. However, how JAK/STAT signaling maintains male GSC fate through its downstream targets remains poorly understood. Here, we identify p115, a tER/cis-Golgi golgin protein, as a putative downstream target of JAK/STAT signaling. p115 maintains GSC fate independent of GM130 and GRASP65. p115 localizes in cytosol, the ER and Golgi apparatus in germline cells and is required for the morphology of the ER and Golgi apparatus. Furthermore, depletion of p115 in GSCs results in aberrant spindle orientation. Mechanistically, p115 associates with and stabilizes STAT. Finally, ectopic expression of STAT completely restores GSC loss caused by p115 depletion. Collectively, JAK/STAT signaling and p115 form a feedforward loop to maintain male GSC fate. Our work provides new insights into the regulatory mechanism of how stem cell maintenance is properly controlled by JAK/STAT signaling.

Citing Articles

A regulatory loop of JAK/STAT signalling and its downstream targets represses cell fate conversion and maintains male germline stem cell niche homeostasis.

Kong R, Zhao H, Li J, Ma Y, Li N, Shi L Cell Prolif. 2024; 57(10):e13648.

PMID: 38987866 PMC: 11471429. DOI: 10.1111/cpr.13648.

Molecular mechanisms of cellular metabolic homeostasis in stem cells.

Li X, Jiang O, Wang S Int J Oral Sci. 2023; 15(1):52.

PMID: 38040705 PMC: 10692173. DOI: 10.1038/s41368-023-00262-z.

References

Wilson P . Centrosome inheritance in the male germ line of Drosophila requires hu-li tai-shao function. Cell Biol Int. 2005; 29(5):360-9. DOI: 10.1016/j.cellbi.2005.03.002. View

Decotto E, Spradling A . The Drosophila ovarian and testis stem cell niches: similar somatic stem cells and signals. Dev Cell. 2005; 9(4):501-10. DOI: 10.1016/j.devcel.2005.08.012. View

Kiger A, Jones D, Schulz C, Rogers M, Fuller M . Stem cell self-renewal specified by JAK-STAT activation in response to a support cell cue. Science. 2001; 294(5551):2542-5. DOI: 10.1126/science.1066707. View

Blanpain C, Fuchs E . Stem cell plasticity. Plasticity of epithelial stem cells in tissue regeneration. Science. 2014; 344(6189):1242281. PMC: 4523269. DOI: 10.1126/science.1242281. View

Leatherman J, DiNardo S . Zfh-1 controls somatic stem cell self-renewal in the Drosophila testis and nonautonomously influences germline stem cell self-renewal. Cell Stem Cell. 2008; 3(1):44-54. PMC: 2601693. DOI: 10.1016/j.stem.2008.05.001. View

Hardy R, Tokuyasu K, LINDSLEY D, Garavito M . The germinal proliferation center in the testis of Drosophila melanogaster. J Ultrastruct Res. 1979; 69(2):180-90. DOI: 10.1016/s0022-5320(79)90108-4. View

Yan R, Small S, Desplan C, Dearolf C, Darnell Jr J . Identification of a Stat gene that functions in Drosophila development. Cell. 1996; 84(3):421-30. DOI: 10.1016/s0092-8674(00)81287-8. View

Issigonis M, Tulina N, de Cuevas M, Brawley C, Sandler L, Matunis E . JAK-STAT signal inhibition regulates competition in the Drosophila testis stem cell niche. Science. 2009; 326(5949):153-6. PMC: 3073347. DOI: 10.1126/science.1176817. View

Davies E, Fuller M . Regulation of self-renewal and differentiation in adult stem cell lineages: lessons from the Drosophila male germ line. Cold Spring Harb Symp Quant Biol. 2009; 73:137-45. DOI: 10.1101/sqb.2008.73.063. View

10.

Binari R, Perrimon N . Stripe-specific regulation of pair-rule genes by hopscotch, a putative Jak family tyrosine kinase in Drosophila. Genes Dev. 1994; 8(3):300-12. DOI: 10.1101/gad.8.3.300. View

11.

Harrison D, Binari R, Nahreini T, Gilman M, Perrimon N . Activation of a Drosophila Janus kinase (JAK) causes hematopoietic neoplasia and developmental defects. EMBO J. 1995; 14(12):2857-65. PMC: 398404. DOI: 10.1002/j.1460-2075.1995.tb07285.x. View

12.

Allan B, Moyer B, Balch W . Rab1 recruitment of p115 into a cis-SNARE complex: programming budding COPII vesicles for fusion. Science. 2000; 289(5478):444-8. DOI: 10.1126/science.289.5478.444. View

13.

de Cuevas M, Matunis E . The stem cell niche: lessons from the Drosophila testis. Development. 2011; 138(14):2861-9. PMC: 3119301. DOI: 10.1242/dev.056242. View

14.

Li X, Luo Y, Yi Y . P115 promotes growth of gastric cancer through interaction with macrophage migration inhibitory factor. World J Gastroenterol. 2014; 19(46):8619-29. PMC: 3870507. DOI: 10.3748/wjg.v19.i46.8619. View

15.

Chandel N, Jasper H, Ho T, Passegue E . Metabolic regulation of stem cell function in tissue homeostasis and organismal ageing. Nat Cell Biol. 2016; 18(8):823-32. DOI: 10.1038/ncb3385. View

16.

Waters M, Clary D, Rothman J . A novel 115-kD peripheral membrane protein is required for intercisternal transport in the Golgi stack. J Cell Biol. 1992; 118(5):1015-26. PMC: 2289595. DOI: 10.1083/jcb.118.5.1015. View

17.

Corwin H, Hanratty W . Characterization of a unique lethal tumorous mutation in Drosophila. Mol Gen Genet. 1976; 144(3):345-7. DOI: 10.1007/BF00341734. View

18.

Flaherty M, Salis P, Evans C, Ekas L, Marouf A, Zavadil J . chinmo is a functional effector of the JAK/STAT pathway that regulates eye development, tumor formation, and stem cell self-renewal in Drosophila. Dev Cell. 2010; 18(4):556-68. PMC: 2859208. DOI: 10.1016/j.devcel.2010.02.006. View

19.

Morrison S, Spradling A . Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell. 2008; 132(4):598-611. PMC: 4505728. DOI: 10.1016/j.cell.2008.01.038. View

20.

Alvarez C, Fujita H, Hubbard A, Sztul E . ER to Golgi transport: Requirement for p115 at a pre-Golgi VTC stage. J Cell Biol. 1999; 147(6):1205-22. PMC: 2168100. DOI: 10.1083/jcb.147.6.1205. View