Sub-nanomolar Sensitive GZnP3 Reveals TRPML1-mediated Neuronal Zn2+ Signals

Authors

Taylor F. Minckley, University of Denver
Chen Zhang, University of Denver
Dylan H. Fudge, University of Denver
Anna M. Dischler, University of Denver
Kate D. LeJeune, University of Denver
Haoxing Xu, The University Of Michigan
Yan Qin, University of DenverFollow

Publication Date

10-22-2019

Document Type

Article

Organizational Units

Biological Sciences

Keywords

Fluorescent Zn2+, Intracellular compartments, Sub-nanomolar, Cytosol

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, sustain longer, and are significantly higher in neurites as compared to the soma. Together, our work not only creates highly sensitive probes for investigating sub-nanomolar Zn2+ dynamics, but also reveals new pools of Zn2+ signals that can play critical roles in neuronal function.

Publication Statement

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Recommended Citation

Minckley, Taylor F, et al. “Sub-Nanomolar Sensitive GZnP3 Reveals TRPML1-Mediated Neuronal Zn2 Signals.” Nature Communications, vol. 10, no. 1, 2019, pp. 1–14. doi: 10.1038/s41467-019-12761-x.