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Duration and magnitude of nerve growth factor signaling depend on the ratio of p75LNTR to TrkA

1998; Wiley; Volume: 51; Issue: 4 Linguagem: Inglês

10.1002/(sici)1097-4547(19980215)51

1097-4547

Jeffery L. Twiss, Hiroshi Wada, Katherine S. Fok, Samuel D.H. Chan, A. Neil Verity, Gregory T. Baxter, Eric M. Shooter, Howard H. Sussman,

NF-κB Signaling Pathways

Journal of Neuroscience ResearchVolume 51, Issue 4 p. 442-453 Duration and magnitude of nerve growth factor signaling depend on the ratio of p75LNTR to TrkA† Jeffery L. Twiss, Corresponding Author Jeffery L. Twiss Department of Pathology and Laboratory Medicine, UCLA Medical Center, Los Angeles, CaliforniaDepartment of Pathology and Laboratory Medicine, UCLA Medical Center, 10833 Le Conte Avenue, 13-317 CHS, Los Angeles, CA 90095-1732Search for more papers by this authorH. Garrett Wada, H. Garrett Wada Department of Research and Development, Molecular Devices Corporation, Sunnyvale, CaliforniaSearch for more papers by this authorKatherine S. Fok, Katherine S. Fok Department of Research and Development, Molecular Devices Corporation, Sunnyvale, CaliforniaSearch for more papers by this authorSamuel D.H. Chan, Samuel D.H. Chan Department of Research and Development, Molecular Devices Corporation, Sunnyvale, CaliforniaSearch for more papers by this authorA. Neil Verity, A. Neil Verity Department of Neurobiology, Roche Bioscience, Palo Alto, CaliforniaSearch for more papers by this authorGregory T. Baxter, Gregory T. Baxter Department of Research and Development, Molecular Devices Corporation, Sunnyvale, CaliforniaSearch for more papers by this authorEric M. Shooter, Eric M. Shooter Department of Neurobiology, Stanford University School of Medicine, Stanford, CaliforniaSearch for more papers by this authorHoward H. Sussman, Howard H. Sussman Department of Pathology, Stanford University School of Medicine, Stanford, CaliforniaSearch for more papers by this author Jeffery L. Twiss, Corresponding Author Jeffery L. Twiss Department of Pathology and Laboratory Medicine, UCLA Medical Center, Los Angeles, CaliforniaDepartment of Pathology and Laboratory Medicine, UCLA Medical Center, 10833 Le Conte Avenue, 13-317 CHS, Los Angeles, CA 90095-1732Search for more papers by this authorH. Garrett Wada, H. Garrett Wada Department of Research and Development, Molecular Devices Corporation, Sunnyvale, CaliforniaSearch for more papers by this authorKatherine S. Fok, Katherine S. Fok Department of Research and Development, Molecular Devices Corporation, Sunnyvale, CaliforniaSearch for more papers by this authorSamuel D.H. Chan, Samuel D.H. Chan Department of Research and Development, Molecular Devices Corporation, Sunnyvale, CaliforniaSearch for more papers by this authorA. Neil Verity, A. Neil Verity Department of Neurobiology, Roche Bioscience, Palo Alto, CaliforniaSearch for more papers by this authorGregory T. Baxter, Gregory T. Baxter Department of Research and Development, Molecular Devices Corporation, Sunnyvale, CaliforniaSearch for more papers by this authorEric M. Shooter, Eric M. Shooter Department of Neurobiology, Stanford University School of Medicine, Stanford, CaliforniaSearch for more papers by this authorHoward H. Sussman, Howard H. Sussman Department of Pathology, Stanford University School of Medicine, Stanford, CaliforniaSearch for more papers by this author First published: 07 December 1998 https://doi.org/10.1002/(SICI)1097-4547(19980215)51:4 3.0.CO;2-CCitations: 21 † Jeffery L. Twiss and H. Garrett Wada contributed equally to this article. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract The role of the low affinity neurotrophin receptor p75LNTR in neurotrophin signal transduction remains open. Recent reports show that this receptor generates intracellular signals independent of Trk activity, and others imply that it collaborates with Trk(s) to enhance cellular responses to low neurotrophin concentrations. We have used the Cytosensor microphysiometer as a direct marker of intracellular metabolic activity to address the physiologic role of p75LNTR in nerve growth factor (NGF) signal transduction. NGF treatment of PC12 or TrkA-transfected Chinese hamster ovary (CHO) cells results in a rapid, transient increase in the extracellular acidification rate as measured by the Cytosensor; in both cell types, p75LNTR enhances this response. p75LNTR affects both the magnitude of and the duration of the extracellular acidification response to NGF. Moreover, it is not merely the presence of p75LNTR, but also the ratio of p75LNTR:TrkA which determines cellular responsiveness to NGF. In transiently transfected CHO cells, a 5:1 ratio of p75LNTR:trkA cDNAs produced the greatest change in NGF-induced acid secretion. Pretreatment of PC12 cells with anti-p75LNTR antibodies decreased the responsiveness to NGF. However, long-term NGF exposure to PC12 cells in which p75LNTR expression was decreased to approximately 10% of wild-type levels showed a longer duration of acid secretion compared to wild-type PC12 cells. Together, these data suggest that p75LNTR may play a dual role in modulating NGF signal transduction by enhancing and extending cellular responses to short-term ligand exposures while attenuating the metabolic response to long-term ligand exposures. With regard to potential Trk-independent p75LNTR signal transduction mechanisms, we detected no change in extracellular acidification response in 75LNTR-transfected CHO cells, PCNA-15 fibroblasts, or Schwann cells, all of which express large amounts of p75LNTR and no Trk. Thus, p75LNTR cannot produce any signal detected by microphysiometry in the absence of TrkA. J. Neurosci. Res. 51:442–453, 1998. © 1998 Wiley-Liss, Inc. Citing Literature Volume51, Issue415 February 1998Pages 442-453 RelatedInformation