Polyglutamine expansion in huntingtin increases its insertion into lipid bilayers.
An expanded polyglutamine (Q) tract (>37Q) in huntingtin (htt) causes Huntington disease. Htt associates with membranes and polyglutamine expansion in htt may alter membrane function in Huntington disease through a mechanism that is not known. Here we used differential scanning calorimetry to examine the effects of polyQ expansion in htt on its insertion into lipid bilayers. We prepared synthetic lipid vesicles composed of phosphatidylcholine and phosphatidylethanolamine and tested interactions of htt amino acids 1-89 with 20Q, 32Q or 53Q with the vesicles. GST-htt1-89 with 53Q inserted into synthetic lipid vesicles significantly more than GST-htt1-89 with 20Q or 32Q. We speculate that by inserting more into cell membranes, mutant huntingtin could increase disorder within the lipid bilayer and thereby disturb cellular membrane function.
Kegel
Kimberly B
KB
Department of Neurology, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA. kkegel@partners.org
Schewkunow
Vitali
V
Sapp
Ellen
E
Masso
Nicholas
N
Wanker
Erich E
EE
DiFiglia
Marian
M
Goldmann
Wolfgang H
WH
D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry
C086055:HTT protein, human; D000071058:Huntingtin Protein; D008051:Lipid Bilayers; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C097188:polyglutamine; C483858:phosphatidylethanolamine