HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 48, 48129-48136, November 28, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/48/48129    most recent M300961200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hibbert, A. P. Articles by Murphy, R. A. Search for Related Content PubMed PubMed Citation Articles by Hibbert, A. P. Articles by Murphy, R. A. Social Bookmarking                      What's this?

Neurotrophin-4, Alone or Heterodimerized with Brain-derived Neurotrophic Factor, Is Sorted to the Constitutive Secretory Pathway^*

Andrew P. Hibbert¶, Stephen J. Morris||, Nabil G. Seidah**, and Richard A. Murphy

From the Centre for Neuronal Survival, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada, the Department of Developmental Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada, and ^**Institut de Recherches Cliniques de Montréal, Montreal, Quebec H2W 1R7, Canada

Nerve growth factor and neurotrophin-3 (NT-3) are processed within the constitutive secretory pathway of neurons and neuroendocrine cells and are released continuously in an activity-independent fashion. In contrast, brain-derived neurotrophic factor (BDNF) is processed in the regulated secretory pathway, stored in vesicles, and released in response to neuronal activity, consistent with its role in modulating synaptic plasticity. In this study, we used vaccinia virus infection and transfection methods to monitor the processing and sorting of neurotrophin-4 (NT-4) in AtT-20 cells, which have been used as a model for the sorting of secretory proteins in neurons. Our data show that NT-4 is processed in the constitutive secretory pathway. The molecule is diffusely distributed within the cells and released, soon after being synthesized, in a manner that is not affected by cell depolarization. We further show that NT-4 and BDNF, when co-expressed, can form heterodimers that are constitutively released. In contrast, heterodimers of NT-3 and BDNF have been shown to be released through the regulated secretory pathway. Thus, NT-4, alone or when co-expressed with BDNF, is processed within and secreted by the constitutive secretory pathway.

Received for publication, January 29, 2003 , and in revised form, September 9, 2003.

^* This work was supported by grants from the Canadian Institute of Health Research (to R. A. M. and to N. G. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ Supported by a scholarship from the McGill University (Canada) Trust, UK, and McGill University Faculty of Medicine.

^|| Present address: Head of Cellular Screening, Aegera Therapeutics, 810 Chemin du Golf, Ile des Soeurs, Quebec, Canada.

To whom correspondence should be addressed: The Salk Institute for Biological Sciences, Office of the President, 10010 N. Torrey Pines Rd., La Jolla, CA 92037. Tel.: 858-453-2480; Fax: 858-546-0838; E-mail: murphy{at}salk.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. Bartkowska, A. Paquin, A. S. Gauthier, D. R. Kaplan, and F. D. Miller Trk signaling regulates neural precursor cell proliferation and differentiation during cortical development Development, December 15, 2007; 134(24): 4369 - 4380. [Abstract] [Full Text] [PDF]

				T. Brigadski, M. Hartmann, and V. Lessmann Differential Vesicular Targeting and Time Course of Synaptic Secretion of the Mammalian Neurotrophins J. Neurosci., August 17, 2005; 25(33): 7601 - 7614. [Abstract] [Full Text] [PDF]

				Z.-Y. Chen, A. Ieraci, H. Teng, H. Dall, C.-X. Meng, D. G. Herrera, A. Nykjaer, B. L. Hempstead, and F. S. Lee Sortilin Controls Intracellular Sorting of Brain-Derived Neurotrophic Factor to the Regulated Secretory Pathway J. Neurosci., June 29, 2005; 25(26): 6156 - 6166. [Abstract] [Full Text] [PDF]

				M. J. Wirth, S. Patz, and P. Wahle Transcellular induction of neuropeptide Y expression by NT4 and BDNF PNAS, February 22, 2005; 102(8): 3064 - 3069. [Abstract] [Full Text] [PDF]

				Z.-Y. Chen, P. D. Patel, G. Sant, C.-X. Meng, K. K. Teng, B. L. Hempstead, and F. S. Lee Variant Brain-Derived Neurotrophic Factor (BDNF) (Met66) Alters the Intracellular Trafficking and Activity-Dependent Secretion of Wild-Type BDNF in Neurosecretory Cells and Cortical Neurons J. Neurosci., May 5, 2004; 24(18): 4401 - 4411. [Abstract] [Full Text] [PDF]