Adam D. Linstedt
Professor
Address:
238 Mellon Institute
Department of Biological Sciences
Carnegie Mellon University
4400 Fifth Avenue
Pittsburgh, PA 15213
Phone: 412-268-1249
Fax: 412-268-7129
Education
Ph.D., University of California, San Francisco
Postdoctoral Appointment, Biozentrum, University of Basel
Research
The research interest in the lab pertains to molecular mechanisms that establish and maintain the membrane bounded subcellular compartments of the secretory and endocytic pathways. This research area continues to be highly significant in terms of basic cell biology. It is also critical to understanding and treating human diseases such as cystic fibrosis, human immunodeficiency virus infection, and cancer.
Ongoing projects include: understanding the mode and mechanism of biogenesis of the Golgi apparatus, understanding the regulatory reactions that impinge on vesicle trafficking machinery to cause disassembly and reassembly of the Golgi apparatus during cell division, and understanding the interactions that occur within the Golgi and endocytic vesicle lumen to govern cell surface-to-Golgi trafficking of proteins and invasive toxins.
These projects are carried out in mammalian tissue culture cells using permeabilized cell assays, biochemical reconstitutions, cell imaging techniques and molecular genetic experiments.
Publications
Forrester A, Rathjen SJ, Daniela Garcia-Castillo M, Bachert C, Couhert A, Tepshi L, Pichard S, Martinez J, Munier M, Sierocki R, Renard HF, Augusto Valades-Cruz C, Dingli F, Loew D, Lamaze C, Cintrat JC, Linstedt AD, Gillet D, Barbier J, Johannes L. Functional dissection of the retrograde Shiga toxin trafficking inhibitor Retro-2. Nat Chem Biol. 2020 Mar;16(3):327-336. doi: 10.1038/s41589-020-0474-4. Epub 2020 Feb 17. PMID: 32080624
Simon EJ, Linstedt AD. Site-specific glycosylation of Ebola virus glycoprotein by human polypeptide GalNAc-transferase 1 induces cell adhesion defects. J Biol Chem. 2018 Dec 21;293(51):19866-19873. doi: 10.1074/jbc.RA118.005375. Epub 2018 Nov 2. PMID: 30389789
Venkat S, Linstedt AD. Manganese-induced trafficking and turnover of GPP130 is mediated by sortilin. Mol Biol Cell. 2017 Sep 15;28(19):2569-2578. doi: 10.1091/mbc.E17-05-0326. Epub 2017 Aug 2. PMID: 28768823
Song L, Linstedt AD. Inhibitor of ppGalNAc-T3-mediated O-glycosylation blocks cancer cell invasiveness and lowers FGF23 levels. Elife. 2017 Mar 31;6:e24051. doi: 10.7554/eLife.24051. PMID: 28362263
Song L, Bachert C, Linstedt AD. Activity Detection of GalNAc Transferases by Protein-Based Fluorescence Sensors In Vivo. Methods Mol Biol. 2016;1496:123-31. doi: 10.1007/978-1-4939-6463-5_10. PMID: 27632006
Tewari R, Bachert C, Linstedt AD. Induced oligomerization targets Golgi proteins for degradation in lysosomes. Mol Biol Cell. 2015 Dec 1;26(24):4427-37. doi: 10.1091/mbc.E15-04-0207. Epub 2015 Oct 7. PMID: 26446839
Song L, Bachert C, Schjoldager KT, Clausen H, Linstedt AD. Development of Isoform-specific Sensors of Polypeptide GalNAc-transferase Activity. J Biol Chem. 2014 Oct 31
Tewari R, Jarvela T, Linstedt AD. Manganese induces oligomerization to promote down-regulation of the intracellular trafficking receptor used by Shiga toxin. Mol Biol Cell. 2014 Jul 30. pii: mbc.E14-05-1003.
Jarvela TS, Linstedt AD. The Application of KillerRed for Acute Protein Inactivation in Living Cells. Curr Protoc Cytom. 2014 Jul 1;69:12.35.1-12.35.10
Veenendaal T, Jarvela T, Grieve AG, van Es JH, Linstedt AD, Rabouille C. GRASP65 controls the cis Golgi integrity in vivo. Biol Open. 2014 May 2;3(6):431-43.
Jarvela, T. and Linstedt, A.D. (2013). “Isoform-specific tethering links the Golgi ribbon to maintain compartmentalization”, Mol Biol Cell, in press.
Mukhopadhyay, S., Redler, B, and Linstedt, A.D. (2013). “Shiga toxin binding site for host cell receptor GPP130 reveals unexpected divergence in toxin trafficking mechanisms”, Mol Biol Cell, 24:2311-8 PMID 23761068.
Mukhopadhyay, S. and Linstedt, A.D. (2013). Retrograde trafficking of AB5 toxins: mechanisms to therapeutics, J Mol Med, 91:1131-1141. PMID: 23665994.
Bachert, C. and Linstedt, A.D. (2013). “A Sensor of Protein O-Glycosylation Based on Sequential Processing in the Golgi apparatus”, Traffic 14(1):47-56. PMID: 23046148
Yadav S, Puthenveedu MA, Linstedt AD. Golgin-160 recruits the dynein motor to position the Golgi apparatus. Dev. Cell. 23:153-165, 2012.
Jarvela T, Linstedt AD. Golgi GRASPs: Moonlighting membrane tethers. Cell Health and Cytoskeleton 2012. 37-47, 2012.
Truschel ST, Zhang M, Bachert C, Macbeth M, Linstedt AD. Allosteric regulation of GRASP-dependent Golgi membrane tethering by mitotic phosphorylation. J Biol Chem. 287:19870-5, 2012.
Mukhopadhyay S, Linstedt AD. Manganese blocks intracellular trafficking of Shiga Toxin and protects against Shiga-induced death. Science 335:332-335, 2012.
Jarvela T, Linstedt AD. Irradiation-induced protein inactivation reveals Golgi enzyme cycling to cell periphery. J. Cell Sci. 125:973-980, 2012.
Truschel ST, Sengupta D, Foote A, Heroux A, Macbeth M, Linstedt AD. Structure of the membrane tethering GRASP domain reveals a unique PDZ ligand interaction that mediates Golgi biogenesis. J Biol Chem. 286:20125-9, 2011.
Mukhopadhyay S, Linstedt AD. Identification of a gain of function mutation in a Golgi P-type ATPase: implications for Mn2+ homeostasis and detoxification. Proc. Natl. Acad. Sci. USA, 108(2):858-63, 2011.
Sengupta D, Linstedt AD. Control of organelle size: the Golgi apparatus. Annual Review of Cell and Devel., 27:57-77, 2011.
Yadav S, Linstedt AD. Golgi positioning. Cold Spring Harb Perspect Biol, 3(5): ePub, 2011.
Sengupta D, Linstedt AD. Mitotic inhibition of GRASP65 organelle tethering involves Polo-like kinase 1 (PLK1) phosphorylation proximate to an internal PDZ ligand. J Biol Chem. 285: 39994-40003, 2010.
Bachert C, Linstedt AD. Dual anchoring of the GRASP membrane tether promotes trans pairing. J Biol Chem. 285: 16294-16301, 2010.
Mukhopadhyay S, Bachert C, Smith D and Linstedt AD. Manganese-induced trafficking and turnover of the cis Golgi glycoprotein GPP130. Mol. Biol. of the Cell, 21: 1282-1292, 2010.
Gong H, Guo Y, Linstedt AD and Schwartz R. Discrete, continuous and stochastic models of protein sorting in the Golgi. Phys Rev E, 81:011914, 2010.
Emr S, Glick BS, Linstedt AD, Lippincott-Schwartz J, Luini A, Malhotra V, Marsh BJ, Nakano A, Pfeffer SR, Rabouille C, Rothman JE, Warren G, and Wieland FT. Journeys through the Golgi—taking stock in a new era. J. Cell Biol. 187: 449-53, 2009.
Sengupta D, Truschel S, Bachert C and Linstedt AD. Organelle tethering by a homotypic PDZ interaction underlies formation of the Golgi membrane network. J. Cell Biol. 186:51-55, 2009.
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