PMID- 17151278
OWN - NLM
STAT- MEDLINE
DCOM- 20061229
LR  - 20200225
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 26
IP  - 49
DP  - 2006 Dec 6
TI  - Mutant huntingtin impairs the post-Golgi trafficking of brain-derived 
      neurotrophic factor but not its Val66Met polymorphism.
PG  - 12748-57
AB  - Brain-derived neurotrophic factor (BDNF) polymorphism is associated with the 
      pathophysiology of several neurodegenerative disorders, including Huntington's 
      disease. In view of these data and the involvement of huntingtin in intracellular 
      trafficking, we examined the intracellular transport and release of Val66Val BDNF 
      (Val-BDNF) and Val66Met BDNF (Met-BDNF) in transfected striatal knock-in cells 
      expressing wild-type or mutant full-length huntingtin. Colocalization studies 
      with specific markers for endoplasmic reticulum showed no differences between the 
      Val-BDNF and Met-BDNF and were not modified by mutant huntingtin. However, 
      post-Golgi trafficking was altered by mutant huntingtin dependent on the BDNF 
      form. Thus, fluorescence recovery after photobleaching (FRAP) and inverse FRAP 
      analysis showed retention of Met-BDNF in the Golgi apparatus with respect to 
      Val-BDNF in wild-type cells. Strikingly, mutant huntingtin diminished post-Golgi 
      trafficking of Val-BDNF, whereas Met-BDNF was not modified. Accordingly, a 
      reduction in the number of transport vesicles was only observed in mutant 
      huntingtin cells transfected with Val-BDNF but not Met-BDNF. Moreover, mutant 
      huntingtin severely affected the KCl-evoked release of Val-BDNF, although it had 
      little effect on Met-BDNF regulated release. The constitutive release of Val-BDNF 
      or Met-BDNF in mutant cells was only slightly reduced. Interestingly, mutant 
      huntingtin only perturbed post-Golgi trafficking of proteins that follow the 
      regulated secretory pathway (epidermal growth factor receptor or atrial 
      natriuretic factor), whereas it did not change those that follow the constitutive 
      pathway (p75(NTR)). We conclude that mutant huntingtin differently affects 
      intracellular transport and release of Val-BDNF and Met-BDNF. In addition, our 
      findings reveal a new role for huntingtin in the regulation of the post-Golgi 
      trafficking of the regulated secretory pathway.
FAU - del Toro, Daniel
AU  - del Toro D
AD  - Departament de Biologia Cel.lular i Anatomia Patologica, Facultat de Medicina, 
      Institut d'Investigacions Biomediques August Pi i Sunyer, Universitat de 
      Barcelona, 08036 Barcelona, Spain.
FAU - Canals, Josep M
AU  - Canals JM
FAU - Gines, Silvia
AU  - Gines S
FAU - Kojima, Masami
AU  - Kojima M
FAU - Egea, Gustavo
AU  - Egea G
FAU - Alberch, Jordi
AU  - Alberch J
LA  - eng
PT  - Comparative Study
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 (HTT protein, human)
RN  - 0 (Huntingtin Protein)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nuclear Proteins)
RN  - AE28F7PNPL (Methionine)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Amino Acid Substitution/genetics
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*genetics/*metabolism
MH  - Cell Line
MH  - Cell Line, Transformed
MH  - Golgi Apparatus/*physiology
MH  - Humans
MH  - Huntingtin Protein
MH  - Huntington Disease/genetics/metabolism
MH  - Methionine/genetics
MH  - Mice
MH  - Mice, Mutant Strains
MH  - *Mutation
MH  - Nerve Tissue Proteins/*genetics/physiology
MH  - Nuclear Proteins/*genetics/physiology
MH  - *Polymorphism, Single Nucleotide
MH  - Protein Transport/genetics
MH  - Signal Transduction/genetics
MH  - Valine/genetics
PMC - PMC6674849
EDAT- 2006/12/08 09:00
MHDA- 2006/12/30 09:00
PMCR- 2007/06/06
CRDT- 2006/12/08 09:00
PHST- 2006/12/08 09:00 [pubmed]
PHST- 2006/12/30 09:00 [medline]
PHST- 2006/12/08 09:00 [entrez]
PHST- 2007/06/06 00:00 [pmc-release]
AID - 26/49/12748 [pii]
AID - 3169893 [pii]
AID - 10.1523/JNEUROSCI.3873-06.2006 [doi]
PST - ppublish
SO  - J Neurosci. 2006 Dec 6;26(49):12748-57. doi: 10.1523/JNEUROSCI.3873-06.2006.