Somshuvra Mukhopadhyay
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View article: NR4A1 is a HIF-dependent repressor of SLC30A10 transcription that controls manganese homeostasis
NR4A1 is a HIF-dependent repressor of SLC30A10 transcription that controls manganese homeostasis Open
The primary mechanism that controls manganese (Mn) homeostasis in mammals is the activation of hypoxia-inducible factor (HIF) transcription factors by elevated Mn, which transcriptionally upregulates expression of the Mn efflux transporter…
View article: Elevated brain manganese induces motor disease by upregulating the kynurenine pathway of tryptophan metabolism
Elevated brain manganese induces motor disease by upregulating the kynurenine pathway of tryptophan metabolism Open
Elevated brain levels of the essential metals manganese (Mn), copper, or iron induce motor disease. However, mechanisms of metal-induced motor disease are unclear and treatments are lacking. Elucidating the mechanisms of Mn-induced motor d…
View article: PHD2 enzyme is an intracellular manganese sensor that initiates the homeostatic response against elevated manganese
PHD2 enzyme is an intracellular manganese sensor that initiates the homeostatic response against elevated manganese Open
Intracellular sensors detect changes in levels of essential metals to initiate homeostatic responses. But, a mammalian manganese (Mn) sensor is unknown, representing a major gap in understanding of Mn homeostasis. Using human-relevant mode…
View article: Elevated thyroid manganese reduces thyroid iodine to induce hypothyroidism in mice, but not rats, lacking SLC30A10 transporter
Elevated thyroid manganese reduces thyroid iodine to induce hypothyroidism in mice, but not rats, lacking SLC30A10 transporter Open
Elevated manganese (Mn) accumulates in the brain and induces neurotoxicity. SLC30A10 is an Mn efflux transporter that controls body Mn levels. We previously reported that full-body Slc30a10 knockout mice (1) recapitulate the body Mn retent…
View article: Loss of SLC30A10 manganese transporter alters expression of neurotransmission genes and activates hypoxia-inducible factor signaling in mice
Loss of SLC30A10 manganese transporter alters expression of neurotransmission genes and activates hypoxia-inducible factor signaling in mice Open
The essential metal manganese (Mn) induces neuromotor disease at elevated levels. The manganese efflux transporter SLC30A10 regulates brain Mn levels. Homozygous loss-of-function mutations in SLC30A10 induce hereditary Mn neurotoxicity in …
View article: Unexpected inhibition of the lipid kinase PIKfyve reveals an epistatic role for p38 MAPKs in endolysosomal fission and volume control
Unexpected inhibition of the lipid kinase PIKfyve reveals an epistatic role for p38 MAPKs in endolysosomal fission and volume control Open
p38 mitogen-activated protein kinases (MAPKs) participate in autophagic signaling; and previous reports suggest that pyridinyl imidazole p38 MAPK inhibitors, including SB203580 and SB202190, induce cell death in some cancer cell-types thro…
View article: Hepatic and intestinal manganese excretion are both required to regulate brain manganese during elevated manganese exposure
Hepatic and intestinal manganese excretion are both required to regulate brain manganese during elevated manganese exposure Open
This article shows that, in contrast with expectations from prior studies and physiological conditions, excretion of manganese by the intestines and liver is equally important in controlling brain manganese during human-relevant manganese …
View article: Unexpected inhibition of the lipid kinase PIKfyve reveals an epistatic role for p38 MAPKs in endolysosomal fission and volume control
Unexpected inhibition of the lipid kinase PIKfyve reveals an epistatic role for p38 MAPKs in endolysosomal fission and volume control Open
p38 mitogen-activated protein kinases (MAPKs) regulate early endocytic trafficking, but their effects on late endocytic trafficking remain unclear. Herein, we report that the pyridinyl imidazole p38 MAPK inhibitors, SB203580 and SB202190, …
View article: SLC30A10 manganese transporter in the brain protects against deficits in motor function and dopaminergic neurotransmission under physiological conditions
SLC30A10 manganese transporter in the brain protects against deficits in motor function and dopaminergic neurotransmission under physiological conditions Open
Loss-of-function mutations in SLC30A10 induce hereditary manganese (Mn)-induced neuromotor disease in humans. We previously identified SLC30A10 to be a critical Mn efflux transporter that controls physiological brain Mn levels by mediating…
View article: A genetically encoded fluorescent sensor for manganese(II), engineered from lanmodulin
A genetically encoded fluorescent sensor for manganese(II), engineered from lanmodulin Open
The design of selective metal-binding sites is a challenge in both small-molecule and macromolecular chemistry. Selective recognition of manganese (II)—the first-row transition metal ion that tends to bind with the lowest affinity to ligan…
View article: Manganese efflux transporter SLC30A10 missense polymorphism T95I associated with liver injury retains manganese efflux activity
Manganese efflux transporter SLC30A10 missense polymorphism T95I associated with liver injury retains manganese efflux activity Open
This study demonstrates that the T95I polymorphism in the manganese transporter SLC30A10, which has been associated with liver disease in human GWAS studies, does not impact transporter function in cell culture. These findings raise doubts…
View article: Activity of the manganese efflux transporter SLC30A10 in dopaminergic but not GABAergic neurons protects against neurotoxicity
Activity of the manganese efflux transporter SLC30A10 in dopaminergic but not GABAergic neurons protects against neurotoxicity Open
Metals such as copper, iron, and manganese (Mn) are essential for life, but induce neurotoxicity at elevated levels. Yet, the neuronal mechanisms of metal-induced neurological disease are largely unclear. A primary limitation has been an i…
View article: Role of excretion in manganese homeostasis and neurotoxicity: a historical perspective
Role of excretion in manganese homeostasis and neurotoxicity: a historical perspective Open
The essential metal manganese (Mn) induces incurable neurotoxicity at elevated levels that manifests as parkinsonism in adults and fine motor and executive function deficits in children. Studies on Mn neurotoxicity have largely focused on …
View article: Up-regulation of the manganese transporter SLC30A10 by hypoxia-inducible factors defines a homeostatic response to manganese toxicity
Up-regulation of the manganese transporter SLC30A10 by hypoxia-inducible factors defines a homeostatic response to manganese toxicity Open
Significance Manganese is an essential metal, but elevated levels cause incurable parkinsonism. A major limitation in treating manganese-induced parkinsonism is a lack of understanding of the mechanisms that regulate levels of manganese in…
View article: A three-pocket model for substrate coordination and selectivity by the nucleotide sugar transporters SLC35A1 and SLC35A2
A three-pocket model for substrate coordination and selectivity by the nucleotide sugar transporters SLC35A1 and SLC35A2 Open
The CMP-sialic acid transporter SLC35A1 and UDP-galactose transporter SLC35A2 are two well-characterized nucleotide sugar transporters with distinctive substrate specificities. Mutations in either induce congenital disorders of glycosylati…
View article: Tamoxifen Derivatives Alter Retromer-Dependent Endosomal Tubulation and Sorting to Block Retrograde Trafficking of Shiga Toxins
Tamoxifen Derivatives Alter Retromer-Dependent Endosomal Tubulation and Sorting to Block Retrograde Trafficking of Shiga Toxins Open
Shiga toxin 1 and 2 (STx1 and STx2) undergo retrograde trafficking to reach the cytosol of cells where they target ribosomes. As retrograde trafficking is essential for disease, inhibiting STx1/STx2 trafficking is therapeutically promising…
View article: Analysis of 1,25-Dihydroxyvitamin D<sub>3</sub> Genomic Action Reveals Calcium-Regulating and Calcium-Independent Effects in Mouse Intestine and Human Enteroids
Analysis of 1,25-Dihydroxyvitamin D<sub>3</sub> Genomic Action Reveals Calcium-Regulating and Calcium-Independent Effects in Mouse Intestine and Human Enteroids Open
Although vitamin D is critical for the function of the intestine, most studies have focused on the duodenum. We show that transgenic expression of the vitamin D receptor (VDR) only in the distal intestine of VDR null mice (KO/TG mice) resu…
View article: Targeting the Early Endosome-to-Golgi Transport of Shiga Toxins as a Therapeutic Strategy
Targeting the Early Endosome-to-Golgi Transport of Shiga Toxins as a Therapeutic Strategy Open
Shiga toxin (STx) produced by Shigella and closely related Shiga toxin 1 and 2 (STx1 and STx2) synthesized by Shiga toxin-producing Escherichia coli (STEC) are bacterial AB5 toxins. All three toxins target kidney cells and may cause life-t…
View article: Brain manganese and the balance between essential roles and neurotoxicity
Brain manganese and the balance between essential roles and neurotoxicity Open
View article: Maintaining Translational Relevance in Animal Models of Manganese Neurotoxicity
Maintaining Translational Relevance in Animal Models of Manganese Neurotoxicity Open
View article: Generation and Validation of Tissue‐Specific Knockout Strains for Toxicology Research
Generation and Validation of Tissue‐Specific Knockout Strains for Toxicology Research Open
Tissue‐specific knockout mice are widely used throughout scientific research. A principle method for generating tissue‐specific knockout mice is the Cre‐ loxP system. Here, we give a detailed description of the steps required to generate a…
View article: Tamoxifen blocks retrograde trafficking of Shiga toxin 1 and 2 and protects against lethal toxicosis
Tamoxifen blocks retrograde trafficking of Shiga toxin 1 and 2 and protects against lethal toxicosis Open
Shiga toxin 1 (STx1) and 2 (STx2), produced by Shiga toxin–producing Escherichia coli , cause lethal untreatable disease. The toxins invade cells via retrograde trafficking. Direct early endosome-to-Golgi transport allows the toxins to eva…
View article: Functional analyses of the UDP-galactose transporter SLC35A2 using the binding of bacterial Shiga toxins as a novel activity assay
Functional analyses of the UDP-galactose transporter SLC35A2 using the binding of bacterial Shiga toxins as a novel activity assay Open
SLC35A2 transports UDP-galactose from the cytosol to the lumen of the Golgi apparatus and endoplasmic reticulum for glycosylation. Mutations in SLC35A2 induce a congenital disorder of glycosylation. Despite the biomedical relevance, mechan…
View article: SLC30A10 transporter in the digestive system regulates brain manganese under basal conditions while brain SLC30A10 protects against neurotoxicity
SLC30A10 transporter in the digestive system regulates brain manganese under basal conditions while brain SLC30A10 protects against neurotoxicity Open
The essential metal manganese becomes neurotoxic at elevated levels. Yet, the mechanisms by which brain manganese homeostasis is regulated are unclear. Loss-of-function mutations in SLC30A10, a cell surface-localized manganese efflux trans…
View article: SLC30A10 Mutation Involved in Parkinsonism Results in Manganese Accumulation within Nanovesicles of the Golgi Apparatus
SLC30A10 Mutation Involved in Parkinsonism Results in Manganese Accumulation within Nanovesicles of the Golgi Apparatus Open
Manganese (Mn) is an essential metal that can be neurotoxic when elevated exposition occurs leading to parkinsonian-like syndromes. Mutations in the Slc30a10 gene have been identified in new forms of familial parkinsonism. SLC30A10 is a ce…
View article: Genome-wide siRNA screen identifies UNC50 as a regulator of Shiga toxin 2 trafficking
Genome-wide siRNA screen identifies UNC50 as a regulator of Shiga toxin 2 trafficking Open
Shiga toxins 1 and 2 (STx1 and STx2) undergo retrograde trafficking to reach the cytosol. Early endosome-to-Golgi transport allows the toxins to evade degradation in lysosomes. Targeting this trafficking step has therapeutic promise, but t…
View article: Hypothyroidism induced by loss of the manganese efflux transporter SLC30A10 may be explained by reduced thyroxine production
Hypothyroidism induced by loss of the manganese efflux transporter SLC30A10 may be explained by reduced thyroxine production Open
SLC30A10 and SLC39A14 are manganese efflux and influx transporters, respectively. Loss-of-function mutations in genes encoding either transporter induce hereditary manganese toxicity. Patients have elevated manganese in the blood and brain…
View article: Familial manganese-induced neurotoxicity due to mutations in SLC30A10 or SLC39A14
Familial manganese-induced neurotoxicity due to mutations in SLC30A10 or SLC39A14 Open
View article: Deficiency in the manganese efflux transporter SLC30A10 induces severe hypothyroidism in mice
Deficiency in the manganese efflux transporter SLC30A10 induces severe hypothyroidism in mice Open
Manganese is an essential metal that becomes toxic at elevated levels. Loss-of-function mutations in SLC30A10, a cell-surface-localized manganese efflux transporter, cause a heritable manganese metabolism disorder resulting in elevated man…
View article: Syndesome Therapeutics for Enhancing Diabetic Wound Healing
Syndesome Therapeutics for Enhancing Diabetic Wound Healing Open
Chronic wounds represent a major healthcare and economic problem worldwide. Advanced wound dressings that incorporate bioactive compounds have great potential for improving outcomes in patients with chronic wounds but significant challenge…