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Lysosome-related organelles contain an expansion compartment that mediates delivery of zinc transporters to promote homeostasis

Mendoza, Adelita D. and Dietrich, Nicholas and Tan, Chieh-Hsiang and Herrera, Daniel and Kasiah, Jennysue and Payne, Zachary and Schneider, Daniel L. and Kornfeld, Kerry (2021) Lysosome-related organelles contain an expansion compartment that mediates delivery of zinc transporters to promote homeostasis. . (Unpublished)

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Lysosome-related organelles play evolutionarily conserved roles in zinc storage, but mechanisms that control zinc flow in and out are not well understood. In C. elegans intestinal cells, the CDF-2 transporter stores zinc in these organelles during excess. Here we identify ZIPT-2.3 as the transporter that releases zinc during deficiency. The expression levels of CDF-2 and ZIPT-2.3 are reciprocally regulated in zinc excess and deficiency, establishing a fundamental mechanism of homeostasis. Super-resolution microscopy demonstrated these organelles are composed of a spherical acidified compartment and a hemispherical expansion compartment. The expansion compartment inflates during zinc excess and deficiency by vesicle fusion delivering zinc transporters. These results identify an unexpected structural feature of lysosome-related organelles that facilitates rapid transitions in the composition of zinc transporters to mediate homeostasis.

Item Type:Report or Paper (Discussion Paper)
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URLURL TypeDescription Paper
Mendoza, Adelita D.0000-0001-8152-3839
Dietrich, Nicholas0000-0002-2068-1283
Tan, Chieh-Hsiang0000-0002-5432-0160
Kasiah, Jennysue0000-0002-6493-5310
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. This version posted September 19, 2021. We thank Laura Kyro for graphics and Suzanne Pfeffer for advice. Confocal/super-resolution data was generated on a Zeiss LSM 880 Airyscan Confocal Microscope which was purchased with support from the Office of Research Infrastructure Programs (ORIP), a part of the NIH Office of the Director under grant OD021629. This research was funded NIH award R01 GM068598 to KK. C.H.T. was a scholar of the McDonnell International Scholars Academy. ADM was supported by the T32HLHL7081training grant. Author Contributions: Conceptualization: A.D.M, N.D., and K.K.; Methodology: A.D.M., N.D., J.T., and K.K.; Formal Analysis: A.D.M., N.D., J.T., and K.K.; Investigation: A.D.M., N.D., J.T., C.C., D.H., J.K., Z.P., D.L.S.; Writing-Original Draft: A.D.M., N.D., and K.K., Writing-Review & Editing: A.D.M., N.D., J.T., C.C., D.H., J.K., Z.P., D.L.S., and K.K.; Visualization: A.D.M., N.D., and J.T.; Supervision: K.K.; Funding acquisition: K.K. The authors declare no competing interests. Data and materials availability: All data is available in the manuscript or supplementary materials.
Funding AgencyGrant Number
NIHR01 GM068598
McDonnell International Scholars AcademyUNSPECIFIED
NIH Predoctoral FellowshipT32HLHL7081
Record Number:CaltechAUTHORS:20210921-195601480
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Official Citation:Lysosome-related organelles contain an expansion compartment that mediates delivery of zinc transporters to promote homeostasis. Adelita D. Mendoza, Nicholas Dietrich, Chieh-Hsiang Tan, Daniel Herrera, Jennysue Kasiah, Zachary Payne, Daniel L. Schneider, Kerry Kornfeld. bioRxiv 2021.09.18.460850; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:110976
Deposited By: Tony Diaz
Deposited On:22 Sep 2021 15:22
Last Modified:16 Nov 2021 19:43

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