A WICB 50th Favorite: Rapid lytic granule convergence to the MTOC in natural killer cells is dependent on dynein but not cytolytic commitment.

Abstract

Molecular Biology of the CellVol. 33, No. 2 ASCB WICB 50th Anniversary FavoriteFree AccessA WICB 50th Favorite: Rapid lytic granule convergence to the MTOC in natural killer cells is dependent on dynein but not cytolytic commitmentAbigail E. Reed and Emily M. MaceAbigail E. ReedDepartment of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032Search for more papers by this author and Emily M. Mace*Address correspondence to: Emily Mace (E-mail Address: [email protected]).Department of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032Search for more papers by this authorErin D Goley, Monitoring EditorPublished Online:18 Jan 2022https://doi.org/10.1091/mbc.E21-04-0218AboutSectionsView PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail To celebrate the 50th anniversary of the American Society for Cell Biology's Women in Cell Biology Committee (WICB), members of WICB and the MBoC Editorial Board invited a diverse group of scientists to highlight MBoC papers by women that have had a scientific or personal impact on the authors of the highlight.Cytotoxic immune cells, including NK cells and T-cells, kill target cells through the mobilization of specialized secretory lysosomes containing perforin and granzymes, termed lytic granules (LG), that undergo directed secretion at the immunological synapse (IS). While polarization of LG had been previously described in concert with polarization of the microtubule- organizing center (MTOC) to the IS, the kinetic mechanisms of LG trafficking to the synapse were poorly understood.We have chosen this article, which has been cited more than 140 times since publication, for the WICB 50 collection to highlight the contribution of women to this study. Namely, three of the four authors were women. In addition, the first author, who was a graduate student and a member of a historically underrepresented group in science, benefited from a training environment in the senior authors’ labs that has continuously supported and promoted women and other underrepresented minority trainees.Using quantitative live cell confocal microscopy and mass spectrometry, the authors demonstrated that LG in human NK cells converged rapidly to the MTOC before its polarization to the IS. Further, this convergence was dependent on minus-ended transport of LG by dynein along microtubules but occurred independently of NK cell commitment to killing (Mentlik et al., 2010). Colocalization of dynein and LG throughout the convergence process, and disruption of this interaction, definitively demonstrated the requirement of dynein for the rapid movement of LG during convergence. This finding, made by a diverse and collaborative investigative team, defined LG convergence as a fundamental priming step for cytotoxicity that increases the efficiency of lytic function by promoting directed secretion.FOOTNOTESDOI:10.1091/mbc.E21-04-0218REFERENCEMentlik AN, Sanborn KB, Holzbaur EL, Orange JS (2010). Rapid lytic granule convergence to the MTOC in natural killer cells is dependent on dynein but not cytolytic commitment. Mol Biol Cell 21, 2241–2256. Link, Google ScholarFiguresReferencesRelatedDetails Vol. 33, No. 2 February 01, 2022 Metrics Downloads & Citations Downloads: 275 History Submitted: 5 November 2021 Revised: 12 November 2021 Accepted: 19 November 2021 Information© 2022 Mace and Reed. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial-Share Alike 4.0 International Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/4.0).PDF download