Molecules and Cells

  • 제46권12호
  • /
  • Pages.757-763
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  • 2023
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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ANKS1A-Deficiency Aberrantly Increases the Entry of the Protein Transport Machinery into the Ependymal Cilia

  • Haeryung Lee (Department of Biological Sciences, Sookmyung Women's University) ;
  • Jiyeon Lee (Department of Biological Sciences, Sookmyung Women's University) ;
  • Miram Shin (Department of Biological Sciences, Sookmyung Women's University) ;
  • Soochul Park (Department of Biological Sciences, Sookmyung Women's University)
  • 투고 : 2023.09.21
  • 심사 : 2023.10.22
  • 발행 : 2023.12.31
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초록

In this study, we examine whether a change in the protein levels for FOP in Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A)-deficient ependymal cells affects the intraflagellar transport (IFT) protein transport system in the multicilia. Three distinct abnormalities are observed in the multicilia of ANKS1A-deficient ependymal cells. First, there were a greater number of IFT88-positive trains along the cilia from ANKS1A deficiency. The results are similar to each isolated cilium as well. Second, each isolated cilium contains a significant increase in the number of extracellular vesicles (ECVs) due to the lack of ANKS1A. Third, Van Gogh-like 2 (Vangl2), a ciliary membrane protein, is abundantly detected along the cilia and in the ECVs attached to them for ANKS1A-deficient cells. We also use primary ependymal culture systems to obtain the ECVs released from the multicilia. Consequently, we find that ECVs from ANKS1A-deficient cells contain more IFT machinery and Vangl2. These results indicate that ANKS1A deficiency increases the entry of the protein transport machinery into the multicilia and as a result of these abnormal protein transports, excessive ECVs form along the cilia. We conclude that ependymal cells make use of the ECV-based disposal system in order to eliminate excessively transported proteins from basal bodies.

키워드

과제정보

This work was supported by grants NRF-2021R1A4A1027355, NRF-2021R1A2C3011919, and NRF-2021R1C1C2009319 from the National Research Foundation of Korea (NRF).

참고문헌

  1. Bloodgood, R.A., Woodward, M.P., and Salomonsky, N.L. (1986). Redistribution and shedding of flagellar membrane glycoproteins visualized using an anti-carbohydrate monoclonal antibody and concanavalin A. J. Cell Biol. 102, 1797-1812. https://doi.org/10.1083/jcb.102.5.1797
  2. Bosch Grau, M., Masson, C., Gadadhar, S., Rocha, C., Tort, O., Marques Sousa, P., Vacher, S., Bieche, I., and Janke, C. (2017). Alterations in the balance of tubulin glycylation and glutamylation in photoreceptors leads to retinal degeneration. J. Cell Sci. 130, 938-949. https://doi.org/10.1242/jcs.199091
  3. Garcia, G., Raleigh, D.R., and Reiter, J.F. (2018). How the ciliary membrane is organized inside-out to communicate outside-in. Curr. Biol. 28, R421-R434. https://doi.org/10.1016/j.cub.2018.03.010
  4. Hong, J.J., Kim, K.E., Park, S.Y., Bok, J., Seo, J.T., and Moon, S.J. (2021). Differential roles of tubby family proteins in ciliary formation and trafficking. Mol. Cells 44, 591-601. https://doi.org/10.14348/molcells.2021.0082
  5. Ishikawa, H. and Marshall, W.F. (2017). Intraflagellar transport and ciliary dynamics. Cold Spring Harb. Perspect. Biol. 9, a021998.
  6. Kanie, T., Abbott, K.L., Mooney, N.A., Plowey, E.D., Demeter, J., and Jackson, P.K. (2017). The CEP19-RABL2 GTPase complex binds IFT-B to initiate intraflagellar transport at the ciliary base. Dev. Cell 42, 22-36.e12. https://doi.org/10.1016/j.devcel.2017.05.016
  7. Lee, H., Noh, H., Mun, J., Gu, C., Sever, S., and Park, S. (2016). Anks1a regulates COPII-mediated anterograde transport of receptor tyrosine kinases critical for tumorigenesis. Nat. Commun. 7, 12799.
  8. Long, H. and Huang, K. (2020). Transport of ciliary membrane proteins. Front. Cell Dev. Biol. 7, 381.
  9. Maguire, J.E., Silva, M., Nguyen, K.C.Q., Hellen, E., Kern, A.D., Hall, D.H., and Barr, M.M. (2015). Myristoylated CIL-7 regulates ciliary extracellular vesicle biogenesis. Mol. Biol. Cell 26, 2823-2832. https://doi.org/10.1091/mbc.E15-01-0009
  10. Malicki, J. and Avidor-Reiss, T. (2014). From the cytoplasm into the cilium: bon voyage. Organogenesis 10, 138-157. https://doi.org/10.4161/org.29055
  11. Nabhan, J.F., Hu, R., Oh, R.S., Cohen, S.N., and Lu, Q. (2012). Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein. Proc. Natl. Acad. Sci. U. S. A. 109, 4146-4151. https://doi.org/10.1073/pnas.1200448109
  12. Nager, A.R., Goldstein, J.S., Herranz-Perez, V., Portran, D., Ye, F., Garcia-Verdugo, J.M., and Nachury, M.V. (2017). An actin network dispatches ciliary GPCRs into extracellular vesicles to modulate signaling. Cell 168, 252-263.e14. https://doi.org/10.1016/j.cell.2016.11.036
  13. Park, S., Lee, H., Lee, J., Park, E., and Park, S. (2019). Ependymal cells require Anks1a for their proper development. Mol. Cells 42, 245-251.
  14. Phua, S.C., Chiba, S., Suzuki, M., Su, E., Roberson, E.C., Pusapati, G.V., Setou, M., Rohatgi, R., Reiter, J.F., Ikegami, K., et al. (2017). Dynamic remodeling of membrane composition drives cell cycle through primary cilia excision. Cell 168, 264-279.e15. https://doi.org/10.1016/j.cell.2016.12.032
  15. Ryu, H., Lee, H., Lee, J., Noh, H., Shin, M., Kumar, V., Hong, S., Kim, J., and Park, S. (2021). The molecular dynamics of subdistal appendages in multi-ciliated cells. Nat. Commun. 12, 612.
  16. Shakya, S. and Westlake, C.J. (2021). Recent advances in understanding assembly of the primary cilium membrane. Fac. Rev. 10, 16.
  17. Taschner, M. and Lorentzen, E. (2016). The intraflagellar transport machinery. Cold Spring Harb. Perspect. Biol. 8, a028092.
  18. Wang, J., Nikonorova, I.A., Silva, M., Walsh, J.D., Tilton, P.E., Gu, A., Akella, J.S., and Barr, M.M. (2021). Sensory cilia act as a specialized venue for regulated extracellular vesicle biogenesis and signaling. Curr. Biol. 31, 3943-3951.e3. https://doi.org/10.1016/j.cub.2021.06.040
  19. Wang, J., Silva, M., Haas, L., Morsci, N., Nguyen, K.Q., Hall, D., and Barr, M. (2014). C. elegans ciliated sensory neurons release extracellular vesicles that function in animal communication. Curr. Biol. 24, 519-525. https://doi.org/10.1016/j.cub.2014.01.002
  20. Wood, C., Huang, K., Diener, D., and Rosenbaum, J. (2013). The cilium secretes bioactive ectosomes. Curr. Biol. 23, 906-911. https://doi.org/10.1016/j.cub.2013.04.019
  21. Wood, C.R. and Rosenbaum, J.L. (2015). Ciliary ectosomes: transmissions from the cell's antenna. Trends Cell Biol. 25, 276-285. https://doi.org/10.1016/j.tcb.2014.12.008