分子與結構細胞生物學
細胞核傳導因子(nuclear transport factor)在細胞核質
轉運活性之外的細胞功能
水溶性的細胞核傳導因子,包括Importin-α和-β,調控物質在細胞核質間
之轉運。對於細胞核之輸入,importins 識別由貨物蛋白所攜帶之細胞核
定位信號(NLS)並與其形成蛋白質複合物,通過核膜上的細胞核孔複合體
(nuclear pore complex)將貨物蛋白從細胞質的一側運送到細胞核的一側。
除了調控細胞核之轉運外,Importin-α和-β 目前也發現可能在調節許多其他
重要的細胞功能。我於2015 年在分生所成立了自己的研究室後,我們採用多
學科方法(包含了生物化學,結構和生物物理方法)來研究核轉運因子如何
調節不同的細胞功能。
γ - 微管蛋白複合物(γ-TuRC)調控微管形成之分子機制
在有絲分裂時,微管組裝形成紡錘體以確認完全無誤的細胞分裂。而在紡錘體
組裝中,微管組織中心(MTOC)(例如中心體)促進了微管新合成,並能夠進
一步在空間和時間上控制著微管形成。除了控制微管形成的數量外,在細胞還
高度調節了微管的極性和動力學性質,以建立不同極性之微管陣列。儘管目前在製備新微管形成的“零件清單”(例如
γ- 微管蛋白複合物(γ-TuRC)及其附著因子)方面已取得了巨大進展,但仍不清楚這些組件如何協同工作以產生新的微
管。因此,我們的研究目標是揭示γ- 微管蛋白複合物調控之微管新合成的分子基礎,其中我們尤其關注微蛋白Mzt1
和Mzt2 如何調節γ-TuRC 在細胞中的位置與促進微管之形成。
- PDF, 2015, Lab. Cell Biology and Chemistry,
The Rockefeller Univ.
- Ph.D., 2009, Lab. Cell Biology, The Rockefeller Univ.
- MS, 2000, Dept. Biochemistry, Natl. Yang-Ming
Univ.
- BS, 1998, Dept. Biology, Fu-Jen Catholic Univ.
- 2015-2018, Newly-Appointment Academic Research Grants of Academia Sinica
- 2015-2018, Young Talent Investigator Recruitment Award, Ministry of Science and Technology
- 2017-2021, Career Development Award
- 2023-2027, Investigator award
- 2023, Academia Sinica Early-Career Investigator Research Achievement Award
Publications arising from my own independent laboratory (Since 2015; corresponding* only)
- Liao, C.C., Wang, Y.S., Pi, W.C., Wang, C.H., Wu, Y.M., Chen, W.Y.*, Hsia, K.C.* (2023). Structural convergence endows nuclear transport receptor Kap114p with a novel transcriptional repressor function toward TATA-box binding protein. Nature Communications 14(1):5518.
- Shankar, S., Hsu, Z.T., Ezquerra, A., Li, C.C., Huang, T.L., Coyaud, E., Viais, R., Grauffel, C., Raught, B. Lim, C., Lüders, J.*, Tsai, S.Y.*, Hsia, K.C.* (2022) A γ-tubulin complex-dependent pathway suppresses ciliogenesis by promoting cilia disassembly. Cell Reports 41(7), 111642.
- Shih, P.Y., Shankar, S., Lee, S.P., Fang, Y.L., Chen, H., Wang, T.F., Hsia, K.C.*, Hsueh, Y.P.* (2022). Zinc-induced phase transition modulates synaptic distribution of autism-linked CTTNBP2. Nature Communications 13(1):2664.
- Chang, C.C., Hsia, K.C.* (2021) More than a zip code: global modulation of cellular function by nuclear localization signals. FEBS J. doi: 10.1111/febs.15659 (Invited review).
- Huang, T.L., Wang, H.J., Chang, Y.C., Wang, S.W., Hsia, K.C.* (2020) Promiscuous binding of microprotein Mozart1 to 𝛾-TuRC mediates specific subcellular localization to control microtubule array formation. Cell Reports 31(13), 107836.
- Wieczork, M., Huang, T.L., Urnavicius, L., Hsia, K.C.*, Kapoor, T.M.* (2020) MZT proteins form multi-faceted structural modules within the 𝛾-tubulin ring complex. Cell Reports 31(13), 107791 (Cover of the issue).
- Liao, C.C., Shankar, S., Pi, W.C., Ahmed, G.R., Chen, W.Y., Hsia, K.C.* (2020) Karyopherin Kap114p-mediated trans-repression controls ribosomal gene expression under saline stress. EMBO reports, 21(7):e48324.
- Chang, C.C., Chen, C.J., Grauffel, C., Pien, Y.C., Lim, C., Tsai, S.Y.*, Hsia, K.C.* (2019) Ran pathway-independent regulation of mitotic Golgi disassembly by Importin-α. Nature Communications 10(1):4307.
- Chang, C.C., Huang, T.L., Shimamoto, Y., Tsai, S.Y., Hsia, K.C.* (2017) Regulation of mitotic spindle assembly factor NuMA by Importin-β. J. Cell Biol. 216(11):3453-3462.
Publications arising from earlier work (First author only)
- Hsia, K.C., Wilson-Kubalek E,M., Dottore A., Hao, Q., Tsai, K.L., Forth S., Shimamoto Y., Milligan, R.A., Kapoor, T.M. (2014) Reconstitution of the augmin complex provides insights into its architecture and function. Nat. Cell Biol. 16(9):852-863 (Cover of the issue).
- Hsia, K.C., Hoelz, A. (2010). “Crystal structure of α-COP in complex with ϵ-COP provides insight into the architecture of the COPI vesicular coat” Proc. Natl. Acad. Sci. 107(25):11271-11276.
- Hsia, K.C., Stavropoulos, P., Blobel, G., Hoelz, A. (2007). “Architecture of a coat for the nuclear pore membrane.” Cell 131(7):1313-1326.
- Hsia, K.C., Chak, K.F., Liang, P.H., Cheng, Y.S., Ku, W.Y., Yuan, H.S. (2004). “DNA binding and degradation by the HNH protein ColE7.” Structure 12(2):205-214.