Magnetic nanoparticle-based isolation of endocytic vesicles reveals a role of the heat shock protein GRP75 in macromolecular delivery.

Proceedings of the National Academy of Sciences of the United States of America
Anders WittrupMattias Belting

Abstract

An increased understanding of cellular uptake mechanisms of macromolecules remains an important challenge in cell biology with implications for viral infection and macromolecular drug delivery. Here, we report a strategy based on antibody-conjugated magnetic nanoparticles for the isolation of endocytic vesicles induced by heparan sulfate proteoglycans (HSPGs), key cell-surface receptors of macromolecular delivery. We provide evidence for a role of the glucose-regulated protein (GRP)75/PBP74/mtHSP70/mortalin (hereafter termed "GRP75") in HSPG-mediated endocytosis of macromolecules. GRP75 was found to be a functional constituent of intracellular vesicles of a nonclathrin-, noncaveolin-dependent pathway that was sensitive to membrane cholesterol depletion and that showed colocalization with the membrane raft marker cholera toxin subunit B. We further demonstrate a functional role of the RhoA GTPase family member CDC42 in this transport pathway; however, the small GTPase dynamin appeared not to be involved. Interestingly, we provide evidence of a functional role of GRP75 using RNAi-mediated down-regulation of GRP75 and GRP75-blocking antibodies, both of which inhibited macromolecular endocytosis. We conclude that GRP75, a chaperone...Continue Reading

References

Aug 22, 1996·International Journal of Cancer. Journal International Du Cancer·A AltmeyerP K Srivastava
Oct 29, 1996·Proceedings of the National Academy of Sciences of the United States of America·K A Mislick, J D Baldeschwieler
Oct 8, 1999·The Biochemical Journal·E MizukoshiT Imamura
Dec 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·Mattias BeltingJeffrey D Esko
Aug 7, 2002·The Journal of Biological Chemistry·Staffan SandgrenMattias Belting
Dec 17, 2002·Cell Stress & Chaperones·Renu WadhwaSunil C Kaul
Dec 21, 2002·The Journal of Biological Chemistry·Bong Kyung ShinSamir M Hanash
Mar 7, 2003·Nature·Sean D Conner, Sandra L Schmid
Mar 14, 2003·Trends in Biochemical Sciences·Mattias Belting
Mar 10, 2004·Proceedings of the National Academy of Sciences of the United States of America·Francois BlondeauPeter S McPherson
Feb 22, 2005·Advanced Drug Delivery Reviews·Mattias BeltingAnders Wittrup
Dec 13, 2005·Nature Cell Biology·Oleg O GlebovBenjamin J Nichols
Sep 16, 2006·The Journal of Biological Chemistry·Motoko UnokiCurtis C Harris
Nov 18, 2006·Cell·Shigeo TakamoriReinhard Jahn
Jan 2, 2007·Biochemical and Biophysical Research Communications·Eun Mi HwangJae-Yong Park
Feb 24, 2007·Nature Reviews. Molecular Cell Biology·Robert G Parton, Kai Simons
Jul 5, 2007·Nature Reviews. Molecular Cell Biology·Satyajit Mayor, Richard E Pagano
Jan 15, 2008·Histochemistry and Cell Biology·Kirsten SandvigBo van Deurs
Mar 7, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Virginia L VegaAntonio De Maio

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Citations

Feb 24, 2012·Gene Therapy·M Nonnenmacher, T Weber
Apr 17, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ayman El-Sayed, Hideyoshi Harashima
May 10, 2011·Nature Nanotechnology·L P McGuinnessL C L Hollenberg
Nov 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Michael B SteketeeJeffrey L Goldberg
Oct 9, 2013·Proceedings of the National Academy of Sciences of the United States of America·Helena C ChristiansonMattias Belting
Jun 22, 2011·Cold Spring Harbor Perspectives in Biology·Stephane SarrazinJeffrey D Esko
Oct 14, 2010·Seminars in Immunopathology·Benjamin Frey, Udo S Gaipl
May 29, 2012·Blood Cells, Molecules & Diseases·Jessica E PrenniChristine S Olver
Nov 27, 2015·Nanomedicine·Elisa SalvatiSilke Krol
Sep 4, 2015·The International Journal of Biochemistry & Cell Biology·Deyan Mihov, Martin Spiess
Oct 23, 2013·Matrix Biology : Journal of the International Society for Matrix Biology·Helena C Christianson, Mattias Belting
Jun 12, 2013·Biotechnology Advances·L BorlidoM R Aires-Barros
May 23, 2017·Nature Communications·Jelka PoharMojca Benčina
Mar 24, 2018·RSC Advances·Alexandra IordachescuLiam M Grover
Nov 14, 2019·Chemical Society Reviews·Mostafa Kamal MasudYusuke Yamauchi
Mar 26, 2013·The Journal of Biological Chemistry·Keyang Chen, Kevin Jon Williams
Nov 22, 2011·Nanotechnology·Cristiana S O PauloLino S Ferreira
Mar 3, 2020·Beilstein Journal of Nanotechnology·Valentina FranciaAnna Salvati
Jul 27, 2021·ASN Neuro·Bipul RayMeena Kishore Sakharkar
Jan 24, 2015·Langmuir : the ACS Journal of Surfaces and Colloids·Mari TakahashiShinya Maenosono

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