Kim S, Jeon TJ, Oberai A, Yang D, Schmidt JJ, Bowie JU.
Transmembrane glycine zippers: physiological and pathological roles in membrane proteins.
Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14278-83.
PubMed.
This news summary states that Dr. Glabe's work weakens the channel hypothesis. On the contrary, I think his work is completely consistent with and supports the basic premise of the model, i.e., membrane disruption and loss of ion homeostasis. Where his work departs from others is that he is seeing a more general membrane disruption rather than defined channels or pores. I view these as all part of the channel hypothesis, however. In my opinion, there is no reason to discount the channel hypothesis (broadly defined) in favor of others at this point and certainly not because Dr. Glabe's work argues against it. Indeed, I think his work actually leads to quite the opposite conclusion.
Reply by Charlie Glabe
With regard to the question of our recent work and the channel
hypothesis, our work supports the general tenet of the channel hypothesis in that
amyloid oligomers permeabilize membranes. The details are different because we do not observe anything that fits the definition of channel. Channels have discrete, unitary conductances, they open and close, they are often directional, and they are generally ion-specific. What we see is more like pores, in the sense that they are
also not ion-selective, but pores typically have a discrete, unitary
conductance, like one pore, two pores, three, etc.
So yes, our results generally support the main thrust of the "channel
hypothesis," but not some of the details.
Comments
University of California, Los Angeles
This news summary states that Dr. Glabe's work weakens the channel hypothesis. On the contrary, I think his work is completely consistent with and supports the basic premise of the model, i.e., membrane disruption and loss of ion homeostasis. Where his work departs from others is that he is seeing a more general membrane disruption rather than defined channels or pores. I view these as all part of the channel hypothesis, however. In my opinion, there is no reason to discount the channel hypothesis (broadly defined) in favor of others at this point and certainly not because Dr. Glabe's work argues against it. Indeed, I think his work actually leads to quite the opposite conclusion.
View all comments by James BowieUniversity of California, Irvine
Reply by Charlie Glabe
With regard to the question of our recent work and the channel
hypothesis, our work supports the general tenet of the channel hypothesis in that
amyloid oligomers permeabilize membranes. The details are different because we do not observe anything that fits the definition of channel. Channels have discrete, unitary conductances, they open and close, they are often directional, and they are generally ion-specific. What we see is more like pores, in the sense that they are
also not ion-selective, but pores typically have a discrete, unitary
conductance, like one pore, two pores, three, etc.
So yes, our results generally support the main thrust of the "channel
View all comments by Charles Glabehypothesis," but not some of the details.
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