PMID- 10818141
OWN - NLM
STAT- MEDLINE
DCOM- 20000615
LR  - 20191023
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 20
IP  - 11
DP  - 2000 Jun 1
TI  - Neurotrophin-3 sorts to the constitutive secretory pathway of hippocampal neurons 
      and is diverted to the regulated secretory pathway by coexpression with 
      brain-derived neurotrophic factor.
PG  - 4059-68
AB  - Hippocampal neurons release nerve growth factor (NGF) through the constitutive 
      secretory pathway, thus allowing the protein to be continuously available for 
      promoting nerve cell survival. In contrast, hippocampal neurons use the regulated 
      secretory pathway to process brain-derived neurotrophic factor (BDNF), which 
      alters synaptic activity when released acutely from dense-core vesicles. Thus, 
      understanding how neurons sort and deliver neurotrophins may provide clues to 
      their functions in brain. In this study, we monitored the processing and delivery 
      of neurotrophin-3 (NT-3). Pulse-chase studies, immunocytochemistry, and 
      secretagogue-induced release experiments were performed on cultured hippocampal 
      neurons and AtT-20 cells infected with vaccinia viruses encoding the NT-3 
      precursor (pro-NT-3). Results show that most newly synthesized NT-3 is released 
      through the constitutive secretory pathway as a result of furin-mediated 
      endoproteolytic cleavage of pro-NT-3 in the trans-Golgi network. Pro-NT-3 can 
      also be diverted into the regulated secretory pathway when cells are treated with 
      alpha1-PDX, a selective inhibitor of furin-like enzymes, or when pro-NT-3 
      expression is increased by transient transfection methods. In cells coinfected 
      with viruses coding for pro-NT-3 and pro-BDNF, NT-3 is sorted into the regulated 
      pathway, stored in secretory granules, and released in response to extracellular 
      cues together with BDNF, apparently as a result of heterodimerization, as 
      suggested by coimmunoprecipitation data. Taken together, these data show that 
      sorting of the NT-3 precursor can occur in both the constitutive and regulated 
      secretory pathways, which is consistent with NT-3 having both survival-promoting 
      and synapse-altering functions.
FAU - Farhadi, H F
AU  - Farhadi HF
AD  - Center for Neuronal Survival, Department of Neurology and Neurosurgery, Montreal 
      Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4.
FAU - Mowla, S J
AU  - Mowla SJ
FAU - Petrecca, K
AU  - Petrecca K
FAU - Morris, S J
AU  - Morris SJ
FAU - Seidah, N G
AU  - Seidah NG
FAU - Murphy, R A
AU  - Murphy RA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neurotrophin 3)
RN  - 0 (alpha 1-Antitrypsin)
RN  - 0 (alpha 1-antitrypsin Portland)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis
MH  - COS Cells
MH  - Cell Survival/physiology
MH  - Cells, Cultured
MH  - Hippocampus/cytology/metabolism/*physiology
MH  - Immunohistochemistry
MH  - Mice
MH  - Microscopy, Confocal
MH  - Neurons/metabolism/*physiology/ultrastructure
MH  - Neurotrophin 3/*biosynthesis/genetics/*physiology
MH  - Precipitin Tests
MH  - Transfection/genetics
MH  - Vaccinia virus/genetics
MH  - alpha 1-Antitrypsin/pharmacology
PMC - PMC6772649
EDAT- 2000/05/20 00:00
MHDA- 2000/06/17 00:00
PMCR- 2000/12/01
CRDT- 2000/05/20 00:00
PHST- 2000/05/20 00:00 [pubmed]
PHST- 2000/06/17 00:00 [medline]
PHST- 2000/05/20 00:00 [entrez]
PHST- 2000/12/01 00:00 [pmc-release]
AID - 20/11/4059 [pii]
AID - 4202 [pii]
AID - 10.1523/JNEUROSCI.20-11-04059.2000 [doi]
PST - ppublish
SO  - J Neurosci. 2000 Jun 1;20(11):4059-68. doi: 10.1523/JNEUROSCI.20-11-04059.2000.