Format

Send to

Choose Destination
J Biol Chem. 2005 Oct 28;280(43):36464-73. Epub 2005 Aug 5.

Huntingtin associates with acidic phospholipids at the plasma membrane.

Author information

1
Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. kegel@helix.mgh.harvard.edu

Abstract

We have identified a domain in the N terminus of huntingtin that binds to membranes. A three-dimensional homology model of the structure of the binding domain predicts helical HEAT repeats, which emanate a positive electrostatic potential, consistent with a charge-based mechanism for membrane association. An amphipathic helix capable of inserting into pure lipid bilayers may serve to anchor huntingtin to the membrane. In cells, N-terminal huntingtin fragments targeted to regions of plasma membrane enriched in phosphatidylinositol 4,5-bisphosphate, receptor bound-transferrin, and endogenous huntingtin. N-terminal huntingtin fragments with an expanded polyglutamine tract aberrantly localized to intracellular regions instead of plasma membrane. Our data support a new model in which huntingtin directly binds membranes through electrostatic interactions with acidic phospholipids.

PMID:
16085648
DOI:
10.1074/jbc.M503672200
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center