A function of huntingtin in guanine nucleotide exchange on Rab11.
Huntingtin is ubiquitously expressed and enriched in the brain. Deletion of the huntingtin gene in mice is lethal during early embryonic development. The function of huntingtin is, however, not clear. Here, we report that huntingtin is important for the function of Rab11, a critical GTPase in regulating membrane traffic from recycling endosomes to the plasma membrane. In huntingtin-null embryonic stem cells, the levels of Rab11 on membranes and nucleotide exchange activity on Rab11 were significantly reduced compared with normal embryonic stem cells. In brain membranes, an antibody against huntingtin immunoprecipitated a nucleotide exchange activity on Rab11 and huntingtin was coprecipitated with Rab11 in the presence of guanosine diphosphate. These data suggest a role for huntingtin in a complex that activates Rab11.
Laboratory of Cellular Neurobiology and Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA. xli12@partners.org
Xueyi
X
Li
Ellen
E
Sapp
Antonio
A
Valencia
Kimberly B
KB
Kegel
Zheng-Hong
ZH
Qin
Jonathan
J
Alexander
Nicholas
N
Masso
Patrick
P
Reeves
James J
JJ
Ritch
Scott
S
Zeitlin
Neil
N
Aronin
Marian
M
Difiglia
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D006150:Guanine Nucleotides / Q000378:metabolism*; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D021381:Protein Transport / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
D006150:Guanine Nucleotides; D008565:Membrane Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C521976:Rab8 protein, mouse; C493231:Slc6a4 protein, mouse