Adam D. Linstedt
Professor
Address:
238 Mellon Institute
Department of Biological Sciences
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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:
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:
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:
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:
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:
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:
Song L, Bachert C, Schjoldager KT, Clausen H, Linstedt AD. Development of Isoform-specific Sensors of Polypeptide GalNAc-transferase Activity.
Tewari R, Jarvela T, Linstedt AD. Manganese induces oligomerization to promote down-regulation of the intracellular trafficking receptor used by Shiga toxin.
Jarvela TS, Linstedt AD. The Application of KillerRed for Acute Protein Inactivation in Living Cells. Curr Protoc Cytom. 20
Veenendaal T, Jarvela T, Grieve AG, van Es JH, Linstedt AD, Rabouille C. GRASP65 controls the cis Golgi integrity in vivo.
Jarvela, T. and Linstedt, A.D. (2013). “Isoform-specific tethering links the Golgi ribbon to maintain compartmentalization”,
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”,
Mukhopadhyay, S. and Linstedt, A.D. (2013). Retrograde trafficking of AB5 toxins: mechanisms to therapeutics,
Bachert, C. and Linstedt, A.D. (2013). “A Sensor of Protein O-Glycosylation Based on Sequential Processing in the Golgi apparatus”,
Yadav S, Puthenveedu MA, Linstedt AD. Golgin-160 recruits the dynein motor to position the Golgi apparatus. .
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. .
Mukhopadhyay S, Linstedt AD. Manganese blocks intracellular trafficking of Shiga Toxin and protects against Shiga-induced death. .
Jarvela T, Linstedt AD. Irradiation-induced protein inactivation reveals Golgi enzyme cycling to cell periphery. .
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. .
Mukhopadhyay S, Linstedt AD. Identification of a gain of function mutation in a Golgi P-type ATPase: implications for Mn2+ homeostasis and detoxification. .
Sengupta D, Linstedt AD. Control of organelle size: the Golgi apparatus. .
Yadav S, Linstedt AD. Golgi positioning. .
Sengupta D, Linstedt AD. Mitotic inhibition of GRASP65 organelle tethering involves Polo-like kinase 1 (PLK1) phosphorylation proximate to an internal PDZ ligand. .
Bachert C, Linstedt AD. Dual anchoring of the GRASP membrane tether promotes trans pairing. .
Mukhopadhyay S, Bachert C, Smith D and Linstedt AD. Manganese-induced trafficking and turnover of the cis Golgi glycoprotein GPP130. .
Gong H, Guo Y, Linstedt AD and Schwartz R. Discrete, continuous and stochastic models of protein sorting in the Golgi. .
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. .
Sengupta D, Truschel S, Bachert C and Linstedt AD. Organelle tethering by a homotypic PDZ interaction underlies formation of the Golgi membrane network. .