Publication Date
10-22-2019
Document Type
Article
Organizational Units
College of Natural Science and Mathematics, 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.
Copyright Date
10-22-2019
Copyright Statement / License for Reuse
This work is licensed under a Creative Commons Attribution 4.0 International License.
Rights Holder
The Authors
Provenance
Received from author
File Format
application/pdf
Language
English (eng)
Extent
14 pgs
File Size
1362 KB
Publication Statement
Copyright is held by the authors. User is responsible for all copyright compliance. This article was originally published as:
Minckley, T. F., Zhang, C., Fudge, D. H., Dischler, A. M., LeJeune, K. D., Xu, H., & Qin, Y. (2019). Sub-nanomolar sensitive GZnP3 reveals TRPML1-mediated neuronal Zn2 signals. Nature Communications, 10(1), 1–14. DOI: 10.1038/s41467-019-12761-x
Publication Title
Nature Communications
Volume
10
Issue
1
First Page
1
Last Page
14
ISSN
2041-1723
Recommended Citation
Minckley, T. F., Zhang, C., Fudge, D. H., Dischler, A. M., LeJeune, K. D., Xu, H., & Qin, Y. (2019). Sub-nanomolar sensitive GZnP3 reveals TRPML1-mediated neuronal Zn2 signals. Nature Communications, 10(1), 1–14. DOI: 10.1038/s41467-019-12761-x