Biometals and glycosylation in humans: Congenital disorders of glycosylation shed lights into the crucial role of Golgi manganese homeostasis

Foulquier, François; Legrand, Dominique

doi:10.1016/j.bbagen.2020.129674

Cited by 31 publications

(32 citation statements)

References 175 publications

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“…Initially believed to be Ca 2+ /H + antiporters that regulate Ca 2+ and pH homeostasis ( Demaegd et al, 2013 ), they were subsequently shown to transport also Mn 2+ ( Stribny et al, 2020 ). This renders them crucial for Golgi-localized Mn 2+ -dependent glycosylation processes ( Potelle et al, 2016 ; Foulquier and Legrand, 2020 ). Interestingly, TMEM165 and GDT1 themselves are sensitive to Mn 2+ and degraded upon elevated levels of cytosolic Mn 2+ ( Potelle et al, 2017 ; Dulary et al, 2018) .…”

Section: Ca 2+ and Mn 2+ In The...mentioning

confidence: 99%

Transport, functions, and interaction of calcium and manganese in plant organellar compartments

Rössner

Hoang

et al. 2021

Plant Physiology

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Calcium (Ca2+) and manganese (Mn2+) are essential elements for plants and have similar ionic radii and binding coordination. They are assigned specific functions within organelles, but share many transport mechanisms to cross organellar membranes. Despite their points of interaction, those elements are usually investigated and reviewed separately. This review takes them out of this isolation. It highlights our current mechanistic understanding and points to open questions of their functions, their transport, and their interplay in the endoplasmic reticulum (ER), vesicular compartments [Golgi apparatus, trans-Golgi Network (TGN), prevacuolar compartment (PVC)], vacuoles, chloroplasts, mitochondria, and peroxisomes. Complex processes demanding these cations, such as Mn2+-dependent glycosylation or systemic Ca2+ signaling, are covered in some detail if they have not been reviewed recently or if recent findings add to current models. The function of Ca2+ as signaling agent released from organelles into the cytosol and within the organelles themselves is a recurrent theme of this review, again keeping the interference by Mn2+ in mind. The involvement of organellar channels [e.g., Glutamate-Receptor-Likes (GLRs), Cyclic-Nucleotide-Gated Channels (CNGCs), Mitochondrial Conductivity Units (MCUs), Two-Pore Channel1 (TPC1)], transporters [e.g., Natural-Resistance-Associated Macrophage Proteins (NRAMPs), Calcium Exchangers (CAXs), Metal-Tolerance Proteins (MTPs), Bivalent-Cation Transporters (BICATs)] and pumps [Autoinhibited Ca2+-ATPases (ACAs), ER Ca2+-ATPases (ECAs)] in the import and export of organellar Ca2+ and Mn2+ is scrutinized, whereby current controversial issues are pointed out. Mechanisms in animals and yeast are taken into account where they may provide a blueprint for processes in plants, in particular with respect to tunable molecular mechanisms of Ca2+-versus-Mn2+ selectivity.

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Section: Ca 2+ and Mn 2+ In The...mentioning

confidence: 99%

Transport, functions, and interaction of calcium and manganese in plant organellar compartments

Rössner

Hoang

et al. 2021

Plant Physiology

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“…Such an effect is possible not only due to compartmentalization, but also the involvement of specific molecular systems for metal storage. The components of the system are mainly metallothioneins and small detoxification molecules containing cysteine [ 83 , 84 ]. It turns out that the Pb content in the dura mater positively correlates with metals such as Mg, P, Ca, Zn, and Ba.…”

Section: Discussionmentioning

confidence: 99%

ICP-MS Multi-Elemental Analysis of the Human Meninges Collected from Sudden Death Victims in South-Eastern Poland

et al. 2022

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Metals perform many important physiological functions in the human body. The distribution of elements in different tissues is not uniform. Moreover, some structures can be the site of an accumulation of essential or toxic metals, leading to multi-directional intracellular damage. In the nervous system, these disorders are especially dangerous. Metals dyshomeostasis has been linked to a variety of neurological disorders which end up leading to permanent injuries. The multi-elemental composition of the human brain is still the subject of numerous investigations and debates. In this study, for the first time, the meninges, i.e., the dura mater and the arachnoid, were examined for their elemental composition by means of inductively coupled plasma mass spectrometry (ICP-MS). Tissue samples were collected post mortem from those who died suddenly as a result of suicide (n = 20) or as a result of injuries after an accident (n = 20). The interactions between 51 elements in both groups showed mainly weak positive correlations, which dominated the arachnoid mater compared to the dura mater. The study showed differences in the distribution of some elements within the meninges in the studied groups. The significant differences concerned mainly metals from the lanthanide family (Ln), macroelements (Na, K, Ca, Mg), a few micronutrients (Co), and toxic cadmium (Cd). The performed evaluation of the elemental distribution in the human meninges sheds new light on the trace metals metabolism in the central nervous system, although we do not yet fully understand the role of the human meninges.

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“…In Hailey-Hailey patient fibroblasts, with impaired ATP2C1 function, TMEM165 becomes more sensitive to extracellular manganese ( Roy et al., 2020 ). TMEM165 loss is associated with congenital disorders of glycosylation, emphasizing the importance of manganese homeostasis in glycosylation ( Foulquier and Legrand, 2020 ). In this regard, a future avenue for discovery would be to examine protein glycosylation patterns in cells exposed to BETi.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide CRISPR-Cas9 screens identify mechanisms of BET bromodomain inhibitor sensitivity

et al. 2021

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Summary BET bromodomain inhibitors hold promise as therapeutic agents in diverse indications, but their clinical progression has been challenging and none have received regulatory approval. Early clinical trials in cancer have shown heterogeneous clinical responses, development of resistance, and adverse events. Increased understanding of their mechanism(s) of action and identification of biomarkers are needed to identify appropriate indication(s) and achieve efficacious dosing. Using genome-wide CRISPR-Cas9 screens at different concentrations, we report molecular mechanisms defining cellular responses to BET inhibitors, some of which appear specific to a single compound concentration. We identify multiple transcriptional regulators and mTOR pathway members as key determinants of JQ1 sensitivity and two Ca 2+ /Mn 2+ transporters, ATP2C1 and TMEM165, as key determinants of JQ1 resistance. Our study reveals new molecular mediators of BET bromodomain inhibitor effects, suggests the involvement of manganese, and provides a rich resource for discovery of biomarkers and targets for combination therapies.

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Biometals and glycosylation in humans: Congenital disorders of glycosylation shed lights into the crucial role of Golgi manganese homeostasis

Cited by 31 publications

References 175 publications

Transport, functions, and interaction of calcium and manganese in plant organellar compartments

Transport, functions, and interaction of calcium and manganese in plant organellar compartments

ICP-MS Multi-Elemental Analysis of the Human Meninges Collected from Sudden Death Victims in South-Eastern Poland

Genome-wide CRISPR-Cas9 screens identify mechanisms of BET bromodomain inhibitor sensitivity

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