Human CNNM2 is not a Mg2+ transporter per se
| Autor: | Stefano Iotti, Jörg R. Aschenbach, Nasrin Abdulhanan, Alina Smorodchenko, Zheng Zhang, Gerhard Sponder, Katharina Wolf, Lucia Mastrototaro, Jürgen Vormann, Andrea Fleig, Lucia Merolle, Reinhold Penner, Martin Kolisek, Katharina Kurth |
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| Přispěvatelé: | Gerhard, Sponder, Mastrototaro, Lucia, Kurth, Katharina, Merolle, Lucia, Zhang, Zheng, Abdulhanan, Nasrin, Smorodchenko, Alina, Wolf, Katharina, Fleig, Andrea, Penner, Reinhold, Iotti, Stefano, Aschenbach, Jörg R, Vormann, Jürgen, Kolisek, Martin |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Transcription Genetic Physiology Clinical Biochemistry Jurkat cells Cell membrane 03 medical and health sciences Jurkat Cells 0302 clinical medicine Physiology (medical) Cell Line Tumor Cyclins Extracellular medicine Homeostasis Humans Magnesium Receptor Cation Transport Proteins Cellular localization biology Membrane transport protein Cell Membrane Membrane Transport Proteins Transporter Biological Transport Cell biology 030104 developmental biology medicine.anatomical_structure HEK293 Cells Magnesium . Homeostasis . Patch clamp . Mag-fura 2 . Protein interactions . Mitochondria Cytoplasm biology.protein 030217 neurology & neurosurgery |
| Popis: | CNNM2 is associated with the regulation of serum Mg concentration, and when mutated, with severe familial hypomagnesemia. The function and cellular localization of CNNM2 and its isomorphs (Iso) remain controversial. The objective of this work was to examine the following: (1) the transcription-responsiveness of CNNM2 to Mg starvation, (2) the cellular localization of Iso1 and Iso2, (3) the ability of Iso1 and Iso2 to transport Mg(2+), and (4) the complex-forming ability and spectra of potential interactors of Iso1 and Iso2. The five main findings are as follows. (1) Mg-starvation induces CNNM2 overexpression that is markedly higher in JVM-13 cells (lymphoblasts) compared with Jurkat cells (T-lymphocytes). (2) Iso1 and Iso2 localize throughout various subcellular compartments in transgenic HEK293 cells overexpressing Iso1 or Iso2. (3) Iso1 and Iso2 do not transport Mg(2+) in an electrogenic or electroneutral mode in transgenic HEK293 cells overexpressing Iso1 or Iso2. (4) Both Iso1 and Iso2 form complexes of a higher molecular order. (5) The spectrum of potential interactors of Iso1 is ten times smaller than that of Iso2. We conclude that sensitivity of CNNM2 expression to extracellular Mg(2+) depletion depends on cell type. Iso1 and Iso2 exhibit a dispersed pattern of cellular distribution; thus, they are not exclusively integral to the cytoplasmic membrane. Iso1 and Iso2 are not Mg(2+) transporters per se. Both isomorphs form protein complexes, and divergent spectra of potential interactors of Iso1 and Iso2 indicate that each isomorph has a distinctive function. CNNM2 is therefore the first ever identified Mg(2+) homeostatic factor without being a Mg(2+) transporter per se. |
| Databáze: | OpenAIRE |
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