Shelli Frey, Gettysburg College
Time:
4:30pm
Location:
CLARK 208
Gettysburg College
Department of Chemistry
Huntington’s disease (HD) is a dominant genetic neurodegenerative disorder associated
with motor and cognitive decline, caused by a mutation in the poly- glutamine
(polyQ) region near the N-terminus of the huntingtin (htt) protein. Expansion
of the polyQ region above 35-40 repeats results in the disease, which is characterized
by inclusion body aggregates of mutated protein. There is increasing evidence
that lipid interactions may play a role in the toxic gain of function associated
with expansion of polyQ in htt, as membrane-related changes (including mutant
htt membrane association and subsequent disruption as well as altered membrane
composition) are observed in HD. The interactions between htt and lipid membranes
were measured with a combination of Langmuir trough monolayer techniques, vesicle
permeability assays, membrane fluctuation analysis, and fluorescence imaging.
Our data suggests that the polyQ flanking regions play a critical role in htt
binding and aggregation on lipid membranes. Additionally, lipid composition strongly
influences htt binding and aggregation and this peptide binding serves to soften
the membrane.