Journal article
CaMKK2 facilitates Golgi-associated vesicle trafficking to sustain cancer cell proliferation
- Abstract:
- Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) regulates cell and whole-body metabolism and supports tumorigenesis. The cellular impacts of perturbing CAMKK2 expression are, however, not yet fully characterised. By knocking down CAMKK2 levels, we have identified a number of significant subcellular changes indicative of perturbations in vesicle trafficking within the endomembrane compartment. To determine how they might contribute to effects on cell proliferation, we have used proteomics to identify Gemin4 as a direct interactor, capable of binding CAMKK2 and COPI subunits. Prompted by this, we confirmed that CAMKK2 knockdown leads to concomitant and significant reductions in δ-COP protein. Using imaging, we show that CAMKK2 knockdown leads to Golgi expansion, the induction of ER stress, abortive autophagy and impaired lysosomal acidification. All are phenotypes of COPI depletion. Based on our findings, we hypothesise that CAMKK2 sustains cell proliferation in large part through effects on organelle integrity and membrane trafficking.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 4.8MB, Terms of use)
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- Publisher copy:
- 10.1038/s41419-021-04335-x
Authors
- Publisher:
- Springer Nature
- Journal:
- Cell Death and Disease More from this journal
- Volume:
- 12
- Article number:
- 1040
- Publication date:
- 2021-11-01
- Acceptance date:
- 2021-10-19
- DOI:
- ISSN:
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2041-4889
- Keywords:
- Pubs id:
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1206235
- Local pid:
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pubs:1206235
- Deposit date:
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2021-11-01
Terms of use
- Copyright holder:
- Stewart et al.
- Copyright date:
- 2021
- Rights statement:
- ©2021 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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