PMID- 23555909
OWN - NLM
STAT- MEDLINE
DCOM- 20130930
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 3
DP  - 2013
TI  - Huntingtin's function in axonal transport is conserved in Drosophila 
      melanogaster.
PG  - e60162
LID - 10.1371/journal.pone.0060162 [doi]
LID - e60162
AB  - Huntington's disease (HD) is a devastating dominantly inherited neurodegenerative 
      disorder caused by an abnormal polyglutamine expansion in the N-terminal part of 
      the huntingtin (HTT) protein. HTT is a large scaffold protein that interacts with 
      more than a hundred proteins and is probably involved in several cellular 
      functions. The mutation is dominant, and is thought to confer new and toxic 
      functions to the protein. However, there is emerging evidence that the mutation 
      also alters HTT's normal functions. Therefore, HD models need to recapitulate 
      this duality if they are to be relevant. Drosophila melanogaster is a useful in 
      vivo model, widely used to study HD through the overexpression of full-length or 
      N-terminal fragments of mutant human HTT. However, it is unclear whether 
      Drosophila huntingtin (DmHTT) shares functions similar to the mammalian HTT. 
      Here, we used various complementary approaches to analyze the function of DmHTT 
      in fast axonal transport. We show that DmHTT interacts with the molecular motor 
      dynein, associates with vesicles and co-sediments with microtubules. DmHTT 
      co-localizes with Brain-derived neurotrophic factor (BDNF)-containing vesicles in 
      rat cortical neurons and partially replaces mammalian HTT in a fast axonal 
      transport assay. DmHTT-KO flies show a reduced fast axonal transport of 
      synaptotagmin vesicles in motoneurons in vivo. These results suggest that the 
      function of HTT in axonal transport is conserved between flies and mammals. Our 
      study therefore validates Drosophila melanogaster as a model to study HTT 
      function, and its dysfunction associated with HD.
FAU - Zala, Diana
AU  - Zala D
AD  - Institut Curie, Orsay, France. diana.zala@curie.fr
FAU - Hinckelmann, Maria-Victoria
AU  - Hinckelmann MV
FAU - Saudou, Frederic
AU  - Saudou F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130328
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Htt protein, Drosophila)
RN  - 0 (Huntingtin Protein)
RN  - 0 (Microtubule-Associated Proteins)
RN  - EC 3.6.4.2 (Dyneins)
SB  - IM
MH  - Animals
MH  - Axonal Transport/*physiology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Line
MH  - Drosophila Proteins
MH  - Drosophila melanogaster/*metabolism
MH  - Dyneins/metabolism
MH  - Humans
MH  - Huntingtin Protein
MH  - Immunoprecipitation
MH  - Microtubule-Associated Proteins/*metabolism
MH  - Microtubules/metabolism
MH  - Neurons/metabolism
MH  - Protein Binding
MH  - Rats
PMC - PMC3610688
COIS- Competing Interests: FS is an Academic Editor at PLOS ONE. This does not alter 
      the authors' adherence to all the PLOS ONE policies on sharing data and 
      materials.
EDAT- 2013/04/05 06:00
MHDA- 2013/10/01 06:00
PMCR- 2013/03/28
CRDT- 2013/04/05 06:00
PHST- 2013/01/29 00:00 [received]
PHST- 2013/02/19 00:00 [accepted]
PHST- 2013/04/05 06:00 [entrez]
PHST- 2013/04/05 06:00 [pubmed]
PHST- 2013/10/01 06:00 [medline]
PHST- 2013/03/28 00:00 [pmc-release]
AID - PONE-D-13-04865 [pii]
AID - 10.1371/journal.pone.0060162 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(3):e60162. doi: 10.1371/journal.pone.0060162. Epub 2013 Mar 28.