Sub-nanomolar sensitive GZnP3 reveals TRPML1-mediated neuronal Zn²⁺ signals.

ABSTRACT: Although numerous fluorescent Zn²⁺ sensors have been reported, it is unclear whether and how Zn²⁺ can be released from the intracellular compartments into the cytosol due to a lack of probes that can detect physiological dynamics of cytosolic Zn²⁺. Here, we create a genetically encoded sensor, GZnP3, which demonstrates unprecedented sensitivity for Zn²⁺ at sub-nanomolar concentrations. Using GZnP3 as well as GZnP3-derived vesicular targeted probes, we provide the first direct evidence that Zn²⁺ can be released from endolysosomal vesicles to the cytosol in primary hippocampal neurons through the TRPML1 channel. Such TRPML1-mediated Zn²⁺ signals are distinct from Ca²⁺ in that they are selectively present in neurons,

SUBMITTER: Minckley TF 

PROVIDER: S-EPMC6805855 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature