Tuning up mitochondria for angiogenesis
نویسنده
چکیده
W ithout voltage-gated sodium channels, heart muscle cells can’t keep a beat. Lowe et al. show how these cells, known as cardiomyocytes, direct channels to the right domain of their plasma membrane. Opening Nav1.5 sodium channels allows an inrush of sodium ions that depolarizes a cardiomyocyte. Patients who carry a faulty version of the channel are at risk for potentially lethal heart arrhythmias. Rather than scattering around the membrane, the channels home in on the junctions between cardiomyocytes. In neurons, the membrane skeletal protein ankyrin-G helps direct sodium channels to specifi c membrane domains, and Lowe et al. tested whether this ankyrin-based pathway performed the same function in heart cells. When the researchers knocked down ankyrin-G using RNAi, they found that Nav1.5 resided around the nucleus instead of in the membrane. The amount of Nav1.5 in the cell also fell, possibly because wayward channels get degraded. After stimulation, cardiac muscle cells lacking ankyrin-G produced a smaller-than-normal current. The knockdown of ankyrin-G had no effect on the location or activity of the cells’ primary voltage-gated calcium channel, suggesting that the targeting pathway in heart cells is specifi c for Nav1.5. By testing mutant forms of ankyrin-G that can’t bind to the channel, the team showed that interactions between the two proteins are necessary to get Nav1.5 into position. The big question now is how ankyrin-G does the job. The protein might haul Nav1.5 to the membrane or stabilize channels that have already made it there.
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ورودعنوان ژورنال:
- The Journal of Cell Biology
دوره 180 شماره
صفحات -
تاریخ انتشار 2008