کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4321055 1291566 2014 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Directionality of Temperature Activation in Mouse TRPA1 Ion Channel Can Be Inverted by Single-Point Mutations in Ankyrin Repeat Six
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Directionality of Temperature Activation in Mouse TRPA1 Ion Channel Can Be Inverted by Single-Point Mutations in Ankyrin Repeat Six
چکیده انگلیسی


• Identified three single-point mutations that make mouse TRPA1 warm activated
• All three mutations are located in ankyrin repeat six
• Mutations do not affect chemical sensitivity
• Biophysical properties of mutants are identical to heat-activated TRP channels

SummarySeveral transient receptor potential (TRP) ion channels are activated with high sensitivity by either cold or hot temperatures. However, structures and mechanism that determine temperature directionality (cold versus heat) are not established. Here we screened 12,000 random mutant clones of the cold-activated mouse TRPA1 ion channel with a heat stimulus. We identified three single-point mutations that are individually sufficient to make mouse TRPA1 warm activated, while leaving sensitivity to chemicals unaffected. Mutant channels have high temperature sensitivity of voltage activation, specifically of channel opening, but not channel closing, which is reminiscent of other heat-activated TRP channels. All mutations are located in ankyrin repeat six, which identifies this domain as a sensitive modulator of thermal activation. We propose that a change in the coupling of temperature sensing to channel gating generates this sensitivity to warm temperatures. Our results demonstrate that minimal changes in protein sequence are sufficient to generate a wide diversity of thermal sensitivities in TRPA1.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 82, Issue 5, 4 June 2014, Pages 1017–1031
نویسندگان
, , , , , , , , , ,