Abstract
It has recently been shown that CTX A3 internalizes into H9C2 cell and targets at mitochondria. It is a temperature-dependent and cholesterol-sensitive process. In order to understand the structure-function correlation of CTX internalization, I employed confocal microscopy to study the internalization of different rhodamine-labeled CTX homologues. My results showed that the amount of internalized CTXs have the tendency of A2 ~ A3 > A1 ~A6. It suggests the ability of CTX internalization may correlate with the loop 1 structure. In addition, CTX treatments under low temperature impaired their internalization, which implies the possible temperature-sensitive pathway involved. Finally, the effect of cholesterol content on their internalization is different for CTX A2 and A3, which suggests the loop 2 structure might play important role. In summary, different cardiotoxins exhibit different behavior as distinguished by either internalized amount or cholesterol sensitivity. Comparison of their primary sequences suggests the loop 1 and loop 2 regions play role in CTX internalization, and the different effects are contributed by their structural diversity.