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 s...

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Autores principales:	Lorna M. Stewart, Lisa Gerner, Mandy Rettel, Frank Stein, James F. Burrows, Ian G. Mills, Emma Evergren
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/6f5b48e9b9844a3a923938136a5be87e
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spelling	oai:doaj.org-article:6f5b48e9b9844a3a923938136a5be87e2021-11-07T12:05:25ZCaMKK2 facilitates Golgi-associated vesicle trafficking to sustain cancer cell proliferation10.1038/s41419-021-04335-x2041-4889https://doaj.org/article/6f5b48e9b9844a3a923938136a5be87e2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04335-xhttps://doaj.org/toc/2041-4889Abstract 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.Lorna M. StewartLisa GernerMandy RettelFrank SteinJames F. BurrowsIan G. MillsEmma EvergrenNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 11, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Lorna M. Stewart Lisa Gerner Mandy Rettel Frank Stein James F. Burrows Ian G. Mills Emma Evergren CaMKK2 facilitates Golgi-associated vesicle trafficking to sustain cancer cell proliferation
description	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.
format	article
author	Lorna M. Stewart Lisa Gerner Mandy Rettel Frank Stein James F. Burrows Ian G. Mills Emma Evergren
author_facet	Lorna M. Stewart Lisa Gerner Mandy Rettel Frank Stein James F. Burrows Ian G. Mills Emma Evergren
author_sort	Lorna M. Stewart
title	CaMKK2 facilitates Golgi-associated vesicle trafficking to sustain cancer cell proliferation
title_short	CaMKK2 facilitates Golgi-associated vesicle trafficking to sustain cancer cell proliferation
title_full	CaMKK2 facilitates Golgi-associated vesicle trafficking to sustain cancer cell proliferation
title_fullStr	CaMKK2 facilitates Golgi-associated vesicle trafficking to sustain cancer cell proliferation
title_full_unstemmed	CaMKK2 facilitates Golgi-associated vesicle trafficking to sustain cancer cell proliferation
title_sort	camkk2 facilitates golgi-associated vesicle trafficking to sustain cancer cell proliferation
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/6f5b48e9b9844a3a923938136a5be87e
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_version_	1718443553356513280

CaMKK2 facilitates Golgi-associated vesicle trafficking to sustain cancer cell proliferation

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