SLC41 Transporters—Molecular Identification and Functional Role

Schweigel-Röntgen, Monika; Kolísek, Martin

doi:10.1016/b978-0-12-800223-0.00011-6

Cited by 30 publications

(25 citation statements)

References 103 publications

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“…Moreover, MgtE variants lacking the N-terminal subdomains showed a reduced Mg 2+ -dependent inhibition and an increased open probability, implicating this subdomain in MgtE function and regulation (Hattori et al, 2009), acting as a sensor of Mg 2+ concentration. In eukaryotic organisms, MgtE-like genes belong to the SCL41 family and their precise role is unknown (Fleig et al, 2013; Schweigel-Röntgen and Kolisek, 2014). Interestingly, the N-terminal regulatory domain of bacterial MgtE is missing in SLC41-A1, thus implying that the eukaryotic transporters evolved different mechanisms of regulation (Schweigel-Röntgen and Kolisek, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…In eukaryotic organisms, MgtE-like genes belong to the SCL41 family and their precise role is unknown (Fleig et al, 2013; Schweigel-Röntgen and Kolisek, 2014). Interestingly, the N-terminal regulatory domain of bacterial MgtE is missing in SLC41-A1, thus implying that the eukaryotic transporters evolved different mechanisms of regulation (Schweigel-Röntgen and Kolisek, 2014). The homology of the soluble portion of C19orf12 with this bacterial subdomain, and its localization in membrane, would support a function for C19orf12 as a regulatory domain of eukaryotic MgtE-like proteins, different from SLC41-A1.…”

Section: Discussionmentioning

confidence: 99%

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Mutations of C19orf12, coding for a transmembrane glycine zipper containing mitochondrial protein, cause mis-localization of the protein, inability to respond to oxidative stress and increased mitochondrial Ca2+

Venco¹,

Bonora

Giorgi

et al. 2015

Front. Genet.

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Mutations in C19orf12 have been identified in patients affected by Neurodegeneration with Brain Iron Accumulation (NBIA), a clinical entity characterized by iron accumulation in the basal ganglia. By using western blot analysis with specific antibody and confocal studies, we showed that wild-type C19orf12 protein was not exclusively present in mitochondria, but also in the Endoplasmic Reticulum (ER) and MAM (Mitochondria Associated Membrane), while mutant C19orf12 variants presented a different localization. Moreover, after induction of oxidative stress, a GFP-tagged C19orf12 wild-type protein was able to relocate to the cytosol. On the contrary, mutant isoforms were not able to respond to oxidative stress. High mitochondrial calcium concentration and increased H2O2 induced apoptosis were found in fibroblasts derived from one patient as compared to controls. C19orf12 protein is a 17 kDa mitochondrial membrane-associated protein whose function is still unknown. Our in silico investigation suggests that, the glycine zipper motifs of C19orf12 form helical regions spanning the membrane. The N- and C-terminal regions with respect to the transmembrane portion, on the contrary, are predicted to rearrange in a structural domain, which is homologs to the N-terminal regulatory domain of the magnesium transporter MgtE, suggesting that C19orf12 may act as a regulatory protein for human MgtE transporters. The mutations here described affect respectively one glycine residue of the glycine zipper motifs, which are involved in dimerization of transmembrane helices and predicted to impair the correct localization of the protein into the membranes, and one residue present in the regulatory domain, which is important for protein-protein interaction.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mutations of C19orf12, coding for a transmembrane glycine zipper containing mitochondrial protein, cause mis-localization of the protein, inability to respond to oxidative stress and increased mitochondrial Ca2+

Venco¹,

Bonora

Giorgi

et al. 2015

Front. Genet.

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“…Studies revealed that, the time course expression change of dZip1, an orthologue of human SLC39 family transporter hZIP1 in Drosophila, was recovered in brains of A42 flies when compared with normal control flies. Researchers assume that modulating the expression level of dZip1 may affect the accumulation of Zn 2＋ in the brain and, accordingly, alter the pathological process of AD [44]. Recently, it has been determined that hippocampusdependent learning and memory functions are not only based on synaptic plasticity of glutamatergic synapses, but also inhibitory GABA-secreting interneurons are required [45].…”

Section: ＋mentioning

confidence: 99%

The Role of the SLC Transporters Protein in the Neurodegenerative Disorders

Ayka¹,

Şehirli²

2020

Clin Psychopharmacol Neurosci

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The solute carrier (SLC) superfamily is one of the major subgroups of membrane proteins in mammalian cells. The solute carrier proteins include more than 400 different membrane-spanning solute carriers organized with 65 families in the human. In solute carrier family neurons, neurotransmitter is considered to be a pharmacological target of neuropsychiatric drugs because of their important role in the recovery of neurotransmitters such as GABA, glutamate, serotonin, dopamine and noradrenaline and regulation of their concentration in synaptic regions. Therefore, solute carrier transporters play vital and different roles in neurodegenerative disorders. In this article, the role of solute carrier transporters in neurodegenerative disorders such as Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, Parkinson's diseases, depression, post-traumatic stress disorder, dementia, schizophrenia, and Epilepsy reviewed and discussed to see how defects or absences in SLC transporter cause neurodegenerative disorders. In this review, we try to summarize what is known about solute carriers with respect to brain distribution and expression. The review summarizes current knowledge on the roles of solute carrier transporters in neurodegenerative disorders.

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“…MgtE belongs to a family of Mg 2+ channels that is ubiquitously distributed in eukaryotes, eubacteria and archaea (Smith et al 1995) (Townsend et al 1995) (Goytain and Quamme 2005) (Sahni and Scharenberg 2013) (Schweigel-Röntgen and Kolisek 2014). The bacterial MgtE is a Mg 2+ -selective ion channel involved in Mg 2+…”

Section: Introductionmentioning

confidence: 99%

Cryo-EM structure of the MgtE Mg²⁺channel pore domain in Mg²⁺-free conditions reveals cytoplasmic pore opening

Jin

Sun

Fujii

et al. 2020

Preprint

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MgtE is a Mg2+ channel conserved in organisms ranging from prokaryotes to eukaryotes, including humans, and plays an important role in Mg2+ homeostasis. The previously determined MgtE structures in the Mg2+-bound, closed state and structure-based functional analyses of MgtE revealed that the binding of Mg2+ ions to the MgtE cytoplasmic domain induces channel inactivation to maintain Mg2+ homeostasis. However, due to the lack of a structure of the MgtE channel, including its transmembrane domain in Mg2+-free conditions, the pore-opening mechanism of MgtE has remained unclear.Here, we determined the cryoelectron microscopy (cryo-EM) structure of the MgtE-Fab complex in the absence of Mg2+ ions. The Mg2+-free MgtE transmembrane domain structure and its comparison with the Mg2+-bound, closed-state structure, together with functional analyses, showed the Mg2+-dependent pore opening of MgtE on the cytoplasmic side and revealed the kink motions of the TM2 and TM5 helices at the glycine residues, which are important for channel activity. Overall, our work provides structure-based mechanistic insights into the channel gating of MgtE.

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SLC41 Transporters—Molecular Identification and Functional Role

Cited by 30 publications

References 103 publications

Mutations of C19orf12, coding for a transmembrane glycine zipper containing mitochondrial protein, cause mis-localization of the protein, inability to respond to oxidative stress and increased mitochondrial Ca2+

Mutations of C19orf12, coding for a transmembrane glycine zipper containing mitochondrial protein, cause mis-localization of the protein, inability to respond to oxidative stress and increased mitochondrial Ca2+

The Role of the SLC Transporters Protein in the Neurodegenerative Disorders

Cryo-EM structure of the MgtE Mg²⁺channel pore domain in Mg²⁺-free conditions reveals cytoplasmic pore opening

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SLC41 Transporters—Molecular Identification and Functional Role

Cited by 30 publications

References 103 publications

Mutations of C19orf12, coding for a transmembrane glycine zipper containing mitochondrial protein, cause mis-localization of the protein, inability to respond to oxidative stress and increased mitochondrial Ca2+

Mutations of C19orf12, coding for a transmembrane glycine zipper containing mitochondrial protein, cause mis-localization of the protein, inability to respond to oxidative stress and increased mitochondrial Ca2+

The Role of the SLC Transporters Protein in the Neurodegenerative Disorders

Cryo-EM structure of the MgtE Mg2+channel pore domain in Mg2+-free conditions reveals cytoplasmic pore opening

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Cryo-EM structure of the MgtE Mg²⁺channel pore domain in Mg²⁺-free conditions reveals cytoplasmic pore opening