Poly-L-glutamine forms cation channels: relevance to the pathogenesis of the polyglutamine diseases.

Abstract:

:We report that long-chain poly-L-glutamine forms cation-selective channels when incorporated into artificial planar lipid bilayer membranes. The channel was permeable to alkali cations and H(+) ions and virtually impermeable to anions; the selectivity sequence based on the single-channel conductance was H(+) > Cs(+) > K(+) > Na(+). The cation channel was characterized by long-lived open states (often lasting for several minutes to tens of minutes) interrupted by brief closings. The appearance of the channel depended critically on the length of polyglutamine chains; ion channels were observed with 40-residue stretches, whereas no significant conductance changes were detected with 29-residue tracts. The channel-forming threshold length of poly-L-glutamine was thus between 29 and 40 residues. A molecular mechanics calculation suggests a mu-helix (. Biophys. J. 69:1130-1141) as a candidate molecular structure of the channel. The channel-forming nature of long-chain poly-L-glutamine may provide a clue to the elucidation of the pathogenetic mechanism of the polyglutamine diseases, a group of inherited neurodegenerative disorders including Huntington's disease.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Monoi H,Futaki S,Kugimiya S,Minakata H,Yoshihara K

doi

10.1016/s0006-3495(00)76830-5

subject

Has Abstract

pub_date

2000-06-01 00:00:00

pages

2892-9

issue

6

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(00)76830-5

journal_volume

78

pub_type

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