Xian Hu

• Guadagno, Noemi Antonella; Margiotta, Azzurra; Bjørnestad, Synne Arstad; Haugen, Linda Hofstad; Kjos, Ingrid; Xiaochun, Xu; Hu, Xian; Bakke, Oddmund; Margadant, Felix Martin & Progida, Cinzia (2020). Rab18 regulates focal adhesion dynamics by interacting with kinectin-1 at the endoplasmic reticulum. Journal of Cell Biology.  ISSN 0021-9525.  219(7), s 1- 23 . doi: 10.1083/JCB.201809020 Fulltekst i vitenarkiv. Vis sammendrag

  The members of the Rab family of small GTPases are molecular switches that regulate distinct steps in different membrane traffic pathways. In addition to this canonical function, Rabs can play a role in other processes, such as cell adhesion and motility. Here, we reveal the role of the small GTPase Rab18 as a positive regulator of directional migration in chemotaxis, and the underlying mechanism. We show that knockdown of Rab18 reduces the size of focal adhesions (FAs) and influences their dynamics. Furthermore, we found that Rab18, by directly interacting with the endoplasmic reticulum (ER)-resident protein kinectin-1, controls the anterograde kinesin-1–dependent transport of the ER required for the maturation of nascent FAs and protrusion orientation toward a chemoattractant. Altogether, our data support a model in which Rab18 regulates kinectin-1 transport toward the cell surface to form ER–FA contacts, thus promoting FA growth and cell migration during chemotaxis

• Hu, Xian; Jalal, Salma; Sheetz, Michael; Bakke, Oddmund & Margadant, Felix Martin (2020). Micro-stepping extended focus reduces photobleaching and preserves structured illumination super-resolution features. Journal of Cell Science.  ISSN 0021-9533.  133, s 1- 12 . doi: 10.1242/jcs.240796 Vis sammendrag

  Despite progress made in confocal microscopy, even fast systems still have insufficient temporal resolution for detailed live-cell volume imaging, such as tracking rapid movement of membrane vesicles in three-dimensional space. Depending on the shortfall, this may result in undersampling and/or motion artifacts that ultimately limit the quality of the imaging data. By sacrificing detailed information in the Z-direction, we propose a new imaging modality that involves capturing fast ‘projections’ from the field of depth and shortens imaging time by approximately an order of magnitude as compared to standard volumetric confocal imaging. With faster imaging, radiation exposure to the sample is reduced, resulting in less fluorophore photobleaching and potential photodamage. The implementation minimally requires two synchronized control signals that drive a piezo stage and trigger the camera exposure. The device generating the signals has been tested on spinning disk confocal and instant structured-illumination-microscopy (iSIM) microscopes. Our calibration images show that the approach provides highly repeatable and stable imaging conditions that enable photometric measurements of the acquired data, in both standard live imaging and super-resolution modes.

• Wu, Hua; Chen, Yuyuan; Li, Bin; Li, Chun; Guo, Jun; You, Jia; Hu, Xian; Kuang, Dong; Qi, Shibo; Pin, Liu; Li, Lei & Xu, Chuanrui (2020). Targeting ROCK1/2 blocks cell division and induces mitotic catastrophe in hepatocellular carcinoma. Biochemical Pharmacology.  ISSN 0006-2952.  184, s 1- 11 . doi: 10.1016/j.bcp.2020.114353
• Hu, Xian; Margadant, Felix Martin; Yao, Mingxi & Sheetz, Michael Patrick (2017). Molecular stretching modulates mechanosensing pathways. Protein Science.  ISSN 0961-8368.  26(7), s 1337- 1351 . doi: 10.1002/pro.3188
• Le, Shimin; Hu, Xian; Yao, Mingxi; Chen, Hu; Yu, Miao; Xu, Xiaochun; Nakazawa, Naotaka; Margadant, Felix Martin; Sheetz, Michael P. & Yan, Jie (2017). Mechanotransmission and Mechanosensing of Human alpha-Actinin 1. Cell reports.  ISSN 2211-1247.  21(10), s 2714- 2723 . doi: 10.1016/j.celrep.2017.11.040
• Hu, Xian; Jing, Chaoran; Xiaochun, Xu; Nakazawa, Naotaka; Cornish, Virginia W.; Margadant, Felix Martin & Sheetz, Michael Patrick (2016). Cooperative Vinculin Binding to Talin Mapped by Time-Resolved Super Resolution MIcorscopy. Nano Letters.  ISSN 1530-6984. . doi: 10.1021/acs.nanolett.6b00650 Vis sammendrag

  The dimeric focal adhesion protein talin contains up to 22 cryptic vinculin binding sites that are exposed by unfolding. Using a novel method to monitor the in situ dynamics of the talin dimer stretch, we find that in contrast to several prevalent talin dimer models the integrin-binding talin N-termini are separated by 162 ± 44 nm on average whereas as expected the C-terminal dimerization domains colocalize and are mobile. Using vinculin tagged by DHFR-TMP Atto655 label, we found that optimal vinculin and vinculin head binding occurred when talin was stretched to 180 nm, while the controls did not bind to talin. Surprisingly, multiple vinculins bound within a single second in narrowly localized regions of the talin rod during stretching. We suggest that talin stretches as an antiparallel dimer and that activates vinculin binding in a cooperative manner, consistent with the stabilization of folded talin by other binding proteins.

• Mingxi, Yao; Goult, Benjamin T.; Klapholz, Benjamin; Hu, Xian; Toseland, Christopher P.; Yingjiang, Guo; Peiwen, Cong; Sheetz, Michael Patrick & Yan, Jie (2016). The Mechanical Response of Talin. Nature Communications.  ISSN 2041-1723. . doi: 10.1038/ncomms11966 Vis sammendrag

  Talin, a force-bearing cytoplasmic adapter essential for integrin-mediated cell adhesion, links the actin cytoskeleton to integrin-based cell–extracellular matrix adhesions at the plasma membrane. Its C-terminal rod domain, which contains 13 helical bundles, plays important roles in mechanosensing during cell adhesion and spreading. However, how the structural stability and transition kinetics of the 13 helical bundles of talin are utilized in the diverse talin-dependent mechanosensing processes remains poorly understood. Here we report the force-dependent unfolding and refolding kinetics of all talin rod domains. Using experimentally determined kinetics parameters, we determined the dynamics of force fluctuation during stretching of talin under physiologically relevant pulling speeds and experimentally measured extension fluctuation trajectories. Our results reveal that force-dependent stochastic unfolding and refolding of talin rod domains make talin a very effective force buffer that sets a physiological force range of only a few pNs in the talin-mediated force transmission pathway.

• Schvartzman, Mark; Palma, Matteo; Sable, Julia; Abramson, Justin; Hu, Xian; Sheetz, Michael Patrick & Wind, Shalom J (2011). Nanolithographic Control of the Spatial Organization of Cellular Adhesion Receptors at the Single- Molecule Level. Nano Letters.  ISSN 1530-6984. . doi: 10.1021/nl104378f
• Zhang, Xin; Tee, YH; Heng, JK; Zhu, Y; Hu, Xian; Margadant, F; Ballestrem, C; Bershadsky, A; Griffiths, Gareth & Yu, H (2010). Kinectin-mediated endoplasmic reticulum dynamics supports focal adhesion growth in the cellular lamella. Journal of Cell Science.  ISSN 0021-9533.  123(22), s 3901- 3912 . doi: 10.1242/jcs.069153

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• Hu, Xian (2020). Biological Applications of MechanoBiology.
• Hu, Xian (2020). First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Xian Hu is first author on ‘Micro-stepping extended focus reduces photobleaching and preserves structured illumination super-resolution features’, published in JCS. Xian is a Postdoc in the lab of Oddmund Bakke at the Department of Biosciences University of Oslo, Norway, investigating the link betw. Journal of Cell Science.  ISSN 0021-9533. . doi: 10.1242/jcs.247320
• Hu, Xian; Bösl, Korbinian & Bakke, Oddmund (2020). How to Manage Microscopy Research Data ELIXIR Norway , BioMedData, NorMIC, NALMIN. Vis sammendrag

  Funding from major funding agencies including the Norwegian Research Council and the European Research Council is now coupled to the successful planning and implementation of Data management. In addition to obtaining funding and get your research published in an high impact factor journal, good data management also yields the potential to make research more efficient, facilitate collaboration and to save time and resources. NALMIN and ELIXIR will host a satellite data management zoom seminar to introduce the following topics. 1. Introduction of data format of optical microscopy data 2. How to make your microscopy based research FAIR (Findable, Accessible, Interoperable and Reusable) and meet the newest requirements of funders and publishers. 3. How to find other FAIR microscopy data for your research. 4. Where to find assistance and/or training on research data management

• Hu, Xian & Margadant, Felix Martin (2020). Methods and Biological Applications of MechanoBiology.
• Xiaochun, Xu; Hu, Xian; Sheetz, Michael Patrick & Margadant, Felix Martin (2017). Distortion Correction for Pillar Tracking Caused by Specimen and Devices.

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