PMID- 12970359
OWN - NLM
STAT- MEDLINE
DCOM- 20040112
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 278
IP  - 48
DP  - 2003 Nov 28
TI  - Neurotrophin-4, alone or heterodimerized with brain-derived neurotrophic factor, 
      is sorted to the constitutive secretory pathway.
PG  - 48129-36
AB  - 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.
FAU - Hibbert, Andrew P
AU  - Hibbert AP
AD  - Centre for Neuronal Survival, Department of Neurology and Neurosurgery, Montreal 
      Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
FAU - Morris, Stephen J
AU  - Morris SJ
FAU - Seidah, Nabil G
AU  - Seidah NG
FAU - Murphy, Richard A
AU  - Murphy RA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030911
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Nerve Growth Factors)
RN  - P658DCA9XD (neurotrophin 4)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/*chemistry
MH  - Cell Line
MH  - Culture Media, Conditioned/pharmacology
MH  - Dimerization
MH  - Glycosylation
MH  - Immunohistochemistry
MH  - Mice
MH  - Microscopy, Fluorescence
MH  - Nerve Growth Factors/biosynthesis/*chemistry
MH  - Neurons/metabolism
MH  - Precipitin Tests
MH  - Protein Transport
MH  - Rats
MH  - Transfection
MH  - Vaccinia virus/genetics
EDAT- 2003/09/13 05:00
MHDA- 2004/01/13 05:00
CRDT- 2003/09/13 05:00
PHST- 2003/09/13 05:00 [pubmed]
PHST- 2004/01/13 05:00 [medline]
PHST- 2003/09/13 05:00 [entrez]
AID - S0021-9258(20)75846-1 [pii]
AID - 10.1074/jbc.M300961200 [doi]
PST - ppublish
SO  - J Biol Chem. 2003 Nov 28;278(48):48129-36. doi: 10.1074/jbc.M300961200. Epub 2003 
      Sep 11.