Functional consequences of the human DMT1 (SLC11A2) mutation on protein expression and iron uptake
We have previously described a case of severe hypochromic microcytic anemia caused by a homozygous mutation in the divalent metal transporter 1 (DMT1 1285G >C). This mutation encodes for an amino acid substitution (E399D) and causes preferential skipping of exon 12 during processing of the DMT1 m...
Gespeichert in:
| Veröffentlicht in: | Blood 2005-12, Vol.106 (12), p.3985-3987 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 3987 |
|---|---|
| container_issue | 12 |
| container_start_page | 3985 |
| container_title | Blood |
| container_volume | 106 |
| creator | Priwitzerova, Monika Nie, Guangjun Sheftel, Alex D. Pospisilova, Dagmar Divoky, Vladimir Ponka, Prem |
| description | We have previously described a case of severe hypochromic microcytic anemia caused by a homozygous mutation in the divalent metal transporter 1 (DMT1 1285G >C). This mutation encodes for an amino acid substitution (E399D) and causes preferential skipping of exon 12 during processing of the DMT1 mRNA. To examine the functional consequences of this mutation, full-length DMT1 transcript with the patient's point mutation or a DMT1 transcript with exon 12 deleted was expressed in Chinese hamster ovary (CHO) cells. Our results demonstrate that the E399D substitution has no effect on protein expression and function. In contrast, deletion of exon 12 led to a decreased expression of the protein and disruption of its subcellular localization and iron uptake activity. We hypothesize that the residual protein in hematopoietic cells represents the functional E399D DMT1 variant, but because of its quantitative reduction, the iron uptake activity of DMT1 in the patient's erythroid cells is severely suppressed. |
| doi_str_mv | 10.1182/blood-2005-04-1550 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_68806984</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006497120669403</els_id><sourcerecordid>68806984</sourcerecordid><originalsourceid>FETCH-LOGICAL-c494t-b54de5f474f335037064716e98b3fdf82e325e6373b4349e98ee18558d70d4833</originalsourceid><addsrcrecordid>eNp9kMFqFTEUhoNY7LX1BVxINoouxp5MkpkMuCm3rQpXXFjXIZOcodGZ5JrMlPr2ZnovdCcEEg7ff_jzEfKawUfGVH3RjzG6qgaQFYiKSQnPyIbJWlUANTwnGwBoKtG17JS8zPkXABO8li_IKWugY0LKDelvlmBnH4MZqY0h458Fg8VM40DnO6R3y2QCvfp2y-j7H7stY5f1Bzots1kztJx9ijP6QPFhnzDndWqCoz6Vx7KfzW88JyeDGTO-Ot5n5OfN9e32S7X7_vnr9nJXWdGJueqlcCgH0YqBcwm8hUa0rMFO9Xxwg6qxdMeGt7wXXHRljsiUlMq14ITi_Iy8O-wtlcov8qwnny2OowkYl6wbpaDplChgfQBtijknHPQ--cmkv5qBXs3qR7N6NatB6NVsCb05bl_6Cd1T5KiyAG-PgMnWjEMywfr8xLW82Fdd4T4dOCwu7j0mna1fnTuf0M7aRf-_Hv8A8dqU3Q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>68806984</pqid></control><display><type>article</type><title>Functional consequences of the human DMT1 (SLC11A2) mutation on protein expression and iron uptake</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Priwitzerova, Monika ; Nie, Guangjun ; Sheftel, Alex D. ; Pospisilova, Dagmar ; Divoky, Vladimir ; Ponka, Prem</creator><creatorcontrib>Priwitzerova, Monika ; Nie, Guangjun ; Sheftel, Alex D. ; Pospisilova, Dagmar ; Divoky, Vladimir ; Ponka, Prem</creatorcontrib><description>We have previously described a case of severe hypochromic microcytic anemia caused by a homozygous mutation in the divalent metal transporter 1 (DMT1 1285G >C). This mutation encodes for an amino acid substitution (E399D) and causes preferential skipping of exon 12 during processing of the DMT1 mRNA. To examine the functional consequences of this mutation, full-length DMT1 transcript with the patient's point mutation or a DMT1 transcript with exon 12 deleted was expressed in Chinese hamster ovary (CHO) cells. Our results demonstrate that the E399D substitution has no effect on protein expression and function. In contrast, deletion of exon 12 led to a decreased expression of the protein and disruption of its subcellular localization and iron uptake activity. We hypothesize that the residual protein in hematopoietic cells represents the functional E399D DMT1 variant, but because of its quantitative reduction, the iron uptake activity of DMT1 in the patient's erythroid cells is severely suppressed.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2005-04-1550</identifier><identifier>PMID: 16091455</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Anemia, Hypochromic - genetics ; Anemias. Hemoglobinopathies ; Animals ; Biological and medical sciences ; Blotting, Western ; Cation Transport Proteins - genetics ; Cation Transport Proteins - metabolism ; CHO Cells ; Cricetinae ; Diseases of red blood cells ; Female ; Fluorescent Antibody Technique ; Hematologic and hematopoietic diseases ; Humans ; Iron - metabolism ; Iron-Binding Proteins - genetics ; Iron-Binding Proteins - metabolism ; Male ; Medical sciences ; Point Mutation ; Transfection</subject><ispartof>Blood, 2005-12, Vol.106 (12), p.3985-3987</ispartof><rights>2005 American Society of Hematology</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c494t-b54de5f474f335037064716e98b3fdf82e325e6373b4349e98ee18558d70d4833</citedby><cites>FETCH-LOGICAL-c494t-b54de5f474f335037064716e98b3fdf82e325e6373b4349e98ee18558d70d4833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17314389$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16091455$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Priwitzerova, Monika</creatorcontrib><creatorcontrib>Nie, Guangjun</creatorcontrib><creatorcontrib>Sheftel, Alex D.</creatorcontrib><creatorcontrib>Pospisilova, Dagmar</creatorcontrib><creatorcontrib>Divoky, Vladimir</creatorcontrib><creatorcontrib>Ponka, Prem</creatorcontrib><title>Functional consequences of the human DMT1 (SLC11A2) mutation on protein expression and iron uptake</title><title>Blood</title><addtitle>Blood</addtitle><description>We have previously described a case of severe hypochromic microcytic anemia caused by a homozygous mutation in the divalent metal transporter 1 (DMT1 1285G >C). This mutation encodes for an amino acid substitution (E399D) and causes preferential skipping of exon 12 during processing of the DMT1 mRNA. To examine the functional consequences of this mutation, full-length DMT1 transcript with the patient's point mutation or a DMT1 transcript with exon 12 deleted was expressed in Chinese hamster ovary (CHO) cells. Our results demonstrate that the E399D substitution has no effect on protein expression and function. In contrast, deletion of exon 12 led to a decreased expression of the protein and disruption of its subcellular localization and iron uptake activity. We hypothesize that the residual protein in hematopoietic cells represents the functional E399D DMT1 variant, but because of its quantitative reduction, the iron uptake activity of DMT1 in the patient's erythroid cells is severely suppressed.</description><subject>Anemia, Hypochromic - genetics</subject><subject>Anemias. Hemoglobinopathies</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Cation Transport Proteins - genetics</subject><subject>Cation Transport Proteins - metabolism</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Diseases of red blood cells</subject><subject>Female</subject><subject>Fluorescent Antibody Technique</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Iron - metabolism</subject><subject>Iron-Binding Proteins - genetics</subject><subject>Iron-Binding Proteins - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Point Mutation</subject><subject>Transfection</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFqFTEUhoNY7LX1BVxINoouxp5MkpkMuCm3rQpXXFjXIZOcodGZ5JrMlPr2ZnovdCcEEg7ff_jzEfKawUfGVH3RjzG6qgaQFYiKSQnPyIbJWlUANTwnGwBoKtG17JS8zPkXABO8li_IKWugY0LKDelvlmBnH4MZqY0h458Fg8VM40DnO6R3y2QCvfp2y-j7H7stY5f1Bzots1kztJx9ijP6QPFhnzDndWqCoz6Vx7KfzW88JyeDGTO-Ot5n5OfN9e32S7X7_vnr9nJXWdGJueqlcCgH0YqBcwm8hUa0rMFO9Xxwg6qxdMeGt7wXXHRljsiUlMq14ITi_Iy8O-wtlcov8qwnny2OowkYl6wbpaDplChgfQBtijknHPQ--cmkv5qBXs3qR7N6NatB6NVsCb05bl_6Cd1T5KiyAG-PgMnWjEMywfr8xLW82Fdd4T4dOCwu7j0mna1fnTuf0M7aRf-_Hv8A8dqU3Q</recordid><startdate>20051201</startdate><enddate>20051201</enddate><creator>Priwitzerova, Monika</creator><creator>Nie, Guangjun</creator><creator>Sheftel, Alex D.</creator><creator>Pospisilova, Dagmar</creator><creator>Divoky, Vladimir</creator><creator>Ponka, Prem</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20051201</creationdate><title>Functional consequences of the human DMT1 (SLC11A2) mutation on protein expression and iron uptake</title><author>Priwitzerova, Monika ; Nie, Guangjun ; Sheftel, Alex D. ; Pospisilova, Dagmar ; Divoky, Vladimir ; Ponka, Prem</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c494t-b54de5f474f335037064716e98b3fdf82e325e6373b4349e98ee18558d70d4833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Anemia, Hypochromic - genetics</topic><topic>Anemias. Hemoglobinopathies</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Cation Transport Proteins - genetics</topic><topic>Cation Transport Proteins - metabolism</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Diseases of red blood cells</topic><topic>Female</topic><topic>Fluorescent Antibody Technique</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Iron - metabolism</topic><topic>Iron-Binding Proteins - genetics</topic><topic>Iron-Binding Proteins - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Point Mutation</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Priwitzerova, Monika</creatorcontrib><creatorcontrib>Nie, Guangjun</creatorcontrib><creatorcontrib>Sheftel, Alex D.</creatorcontrib><creatorcontrib>Pospisilova, Dagmar</creatorcontrib><creatorcontrib>Divoky, Vladimir</creatorcontrib><creatorcontrib>Ponka, Prem</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Priwitzerova, Monika</au><au>Nie, Guangjun</au><au>Sheftel, Alex D.</au><au>Pospisilova, Dagmar</au><au>Divoky, Vladimir</au><au>Ponka, Prem</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional consequences of the human DMT1 (SLC11A2) mutation on protein expression and iron uptake</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2005-12-01</date><risdate>2005</risdate><volume>106</volume><issue>12</issue><spage>3985</spage><epage>3987</epage><pages>3985-3987</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>We have previously described a case of severe hypochromic microcytic anemia caused by a homozygous mutation in the divalent metal transporter 1 (DMT1 1285G >C). This mutation encodes for an amino acid substitution (E399D) and causes preferential skipping of exon 12 during processing of the DMT1 mRNA. To examine the functional consequences of this mutation, full-length DMT1 transcript with the patient's point mutation or a DMT1 transcript with exon 12 deleted was expressed in Chinese hamster ovary (CHO) cells. Our results demonstrate that the E399D substitution has no effect on protein expression and function. In contrast, deletion of exon 12 led to a decreased expression of the protein and disruption of its subcellular localization and iron uptake activity. We hypothesize that the residual protein in hematopoietic cells represents the functional E399D DMT1 variant, but because of its quantitative reduction, the iron uptake activity of DMT1 in the patient's erythroid cells is severely suppressed.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>16091455</pmid><doi>10.1182/blood-2005-04-1550</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-4971 |
| ispartof | Blood, 2005-12, Vol.106 (12), p.3985-3987 |
| issn | 0006-4971 1528-0020 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68806984 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Anemia, Hypochromic - genetics Anemias. Hemoglobinopathies Animals Biological and medical sciences Blotting, Western Cation Transport Proteins - genetics Cation Transport Proteins - metabolism CHO Cells Cricetinae Diseases of red blood cells Female Fluorescent Antibody Technique Hematologic and hematopoietic diseases Humans Iron - metabolism Iron-Binding Proteins - genetics Iron-Binding Proteins - metabolism Male Medical sciences Point Mutation Transfection |
| title | Functional consequences of the human DMT1 (SLC11A2) mutation on protein expression and iron uptake |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T16%3A24%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Functional%20consequences%20of%20the%20human%20DMT1%20(SLC11A2)%20mutation%20on%20protein%20expression%20and%20iron%20uptake&rft.jtitle=Blood&rft.au=Priwitzerova,%20Monika&rft.date=2005-12-01&rft.volume=106&rft.issue=12&rft.spage=3985&rft.epage=3987&rft.pages=3985-3987&rft.issn=0006-4971&rft.eissn=1528-0020&rft_id=info:doi/10.1182/blood-2005-04-1550&rft_dat=%3Cproquest_cross%3E68806984%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=68806984&rft_id=info:pmid/16091455&rft_els_id=S0006497120669403&rfr_iscdi=true |