許家維

姓名：許家維

職稱：專任助理教授

研究室位置：IBS N304

電話：(02)33664068、(02)23665531

Email：jwhsu@ntu.edu.tw

研究領域：細胞生物學、蛋白質運輸與傳遞

期刊論文

期刊論文
學經歷
研究方向

年度	論文名稱
2024	Chu, S.L., Huang, J.R., Chang, Y.T., Yao, S.Y., Yang, J.S., Hsu, W.V., and Hsu, J.W. Phosphoglycerate kinase 1 acts as a cargo adaptor to promote EGFR transport to the lysosome. Nat Commun 15, 1021 (2024).
2022	Chen, K.J.#, Hsu, J.W.# & Lee, F.S. AMPK promotes Arf6 activation in a kinase-independent manner upon glucose starvation. J Cell Sci 135 (2022). (# equal contribution)
2021	Feng, H. P., Cheng, H. Y., Hsiao, T. F., Lin, T. W., Hsu, J. W., Huang, L. H. and Yu, C. J. (2021). ArfGAP1 acts as a GTPase-activating protein for human ADP-ribosylation factor-like 1 protein. FASEB J 35, e21337.
2020	Hsu, J. W., Bai, M., Li, K., Yang, J. S., Chu, N., Cole, P. A., Eck, M. J., Li, J. and Hsu, V. W. (2020) Hsu The protein kinase Akt acts as a coat adaptor in endocytic recycling. Nat Cell Biol in press (* equal contribution)
2019	Yang, J. S., Hsu, J. W., Park, S. Y., Lee, S. Y., Li, J., Bai, M., Alves, C., Tseng, W., Michelet, X., Ho, I. C. and Hsu, V. W. (2019). ALDH7A1 inhibits the intracellular transport pathways during hypoxia and starvation to promote cellular energy homeostasis. Nat Commun 10, 4068.
2018	Yang, J. S., Hsu, J. W., Park, S. Y., Li, J., Oldham, W. M., Beznoussenko, G. V., Mironov, A. A., Loscalzo, J. and Hsu, V. W. (2018). GAPDH inhibits intracellular pathways during starvation for cellular energy homeostasis. Nature 561, 263-267.
2017	Wang, I. H., Chen, Y. J., Hsu, J. W. and Lee, F. J. (2017). The Arl3 and Arl1 GTPases co-operate with Cog8 to regulate selective autophagy via Atg9 trafficking. Traffic 18, 580-589.
2016	Hsu, J. W., Tang, P. H., Wang, I. H., Liu, C. L., Chen, W. H., Tsai, P. C., Chen, K. Y., Chen, K. J., Yu, C. J. and Lee, F. J. (2016). Unfolded protein response regulates yeast small GTPase Arl1p activation at late Golgi via phosphorylation of Arf GEF Syt1p. Proc Natl Acad Sci U S A 113, E1683-90.
2015	Hsu, J. W., Chen, K. J. and Lee, F. J. (2015). Snf1/AMP-activated protein kinase activates Arf3p to promote invasive yeast growth via a non-canonical GEF domain. Nat Commun 6, 7840.
2014	Hsu, J. W., Chen, Z. J., Liu, Y. W. and Lee, F. J. (2014). Mechanism of action of the flippase Drs2p in modulating GTP hydrolysis of Arl1p. J Cell Sci 127, 2615-20.
2013	Hsu, J. W., Chang, L. C., Jang, L. T., Huang, C. F. and Lee, F. J. (2013). The N-terminus of Vps74p is essential for the retention of glycosyltransferases in the Golgi but not for the modulation of apical polarized growth in Saccharomyces cerevisiae. PLoS One 8, e74715.
2013	Hsu, J. W. and Lee, F. J. (2013). Arf3p GTPase is a key regulator of Bud2p activation for invasive growth in Saccharomyces cerevisiae. Mol Biol Cell 24, 2328-39.
2013	Tsai, P. C., Hsu, J. W., Liu, Y. W., Chen, K. Y. and Lee, F. J. (2013). Arl1p regulates spatial membrane organization at the trans-Golgi network through interaction with Arf-GEF Gea2p and flippase Drs2p. Proc Natl Acad Sci U S A 110, E668-77. (Selected in "From the Cover" with a Commentary on page 2691 in issue 8 of volume 110), (Recommended as being of special significance in the "Faculty of 1000")
2011	Hsu, J. W., Huang, H. C., Chen, S. T., Wong, C. H. and Juan, H. F. (2011). Ganoderma lucidum Polysaccharides Induce Macrophage-Like Differentiation in Human Leukemia THP-1 Cells via Caspase and p53 Activation. Evid Based Complement Alternat Med 2011, 358717.
2010	Chen, K. Y., Tsai, P. C., Hsu, J. W., Hsu, H. C., Fang, C. Y., Chang, L. C., Tsai, Y. T., Yu, C. J. and Lee, F. J. (2010). Syt1p promotes activation of Arl1p at the late Golgi to recruit Imh1p. J Cell Sci 123, 3478-89. (Highlighted in the "In this Issue")
2007	Cheng, K. C., Huang, H. C., Chen, J. H., Hsu, J. W., Cheng, H. C., Ou, C. H., Yang, W. B., Chen, S. T., Wong, C. H. and Juan, H. F. (2007). Ganoderma lucidum polysaccharides in human monocytic leukemia cells: from gene expression to network construction. BMC Genomics 8, 411. (Highly accessed)
2005	Wang, H. S., Hung, Y., Su, C. H., Peng, S. T., Guo, Y. J., Lai, M. C., Liu, C. Y. and Hsu, J. W. (2005). CD44 cross-linking induces integrin-mediated adhesion and transendothelial migration in breast cancer cell line by up-regulation of LFA-1 (αLβ2) and VLA-4 (α4β1). Exp Cell Res 304, 116-26.

學校名稱	系所	學位/職稱	期間
國立臺灣大學	生化科學研究所	助理教授	2020-至今
國立臺灣大學	分子醫學研究所	客座專家	2019-2020
美國哈佛醫學院及布萊根婦女醫院		博士後研究員	2015-2019
國立臺灣大學	分子醫學研究所	博士後研究員	2013-2015
國立臺灣大學	分子醫學研究所	博士	2008-2013

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Molecular Mechanism of Protein Transport
My research focuses on how intracellular protein transport is tightly regulated. Coat proteins, which initiate intracellular transport by coupling their roles in the vesicle formation and cargo sorting, are the best described to control the vesicular transport through their abilities to deform the membrane and directly bind to the cargo. ARF6 (ADP-Ribosylation Factor 6) is a small GTPase functioning in the regulation of endocytic recycling. Previously, I already defined the cargo adaptors, ACAP1 and AKT, both required for the endocytic recycling. ACAP1 (ARFGAP with Coil-coil, Ankyrin repeat and PH domain 1) is a GAP (GTPase-Activating Protein) for ARF6 to promote GTP hydrolysis of ARF6 and therefore to release ARF6 from the membrane. AKT is a serine/threonine kinase involving in many cellular processes, such as cell growth and migration. Although ACAP1 and AKT work together to regulate endocytic recycling, however, the upstream signaling that facilitates ACAP1 and AKT for the function of endocytic recycling remains unclear. In addition, how ACAP1 and AKT cooperate each other to form the complex for cargo sorting still needs to be resolved. These functional studies on the coat protein complexes will shed molecular insights into key physiologic and pathologic events, such as cell growth and migration.

Cargo Sorting during Vesicle Formation
Coat proteins play a major role in vesicular transport by binding to cargoes and sorting into intracellular compartment. Cargo recognition is mediated by components of the coat complex known as adaptor proteins. We previously showed that Arf-GAP with coil-coil, ANK repeat and PH domain-containing protein 1 (ACAP1) functions as an adaptor for a clathrin coat complex to regulate endocytic recycling. We further demonstrated that the protein kinase Akt acts as a co-adaptor in this complex to promote their recycling. This is a fundamentally different function in which Akt kinase acts as an effector rather than a regulator in a cellular event.

Phosphorylation of PGK1 on S203 promotes its recruitment to endosomal membranes where it acts as a cargo adaptor to recognize the dileucine sorting motif on EGFR to accelerate its transport to the lysosome. This phosphorylation promotes PGK1 recruitment to endosomal membranes in two complementary ways, a protein-based mechanism that involves binding to hepatocyte growth factor receptor substrate (Hrs) and a lipid-based mechanism that involves binding to PI(4,5)P2. These findings not only reveal a previously unknown role of a metabolic enzyme, but also advance the mechanistic understanding of how endocytic EGFR is transported to the lysosome.