Myotonic dystrophy kinase‐related CDC42‐binding kinase α, a new transferrin receptor type 2‐binding partner, is a regulator of erythropoiesis
Efficient erythropoiesis relies on the expression of the transferrin receptor type 2 (TFR2). In erythroid precursors, TFR2 facilitates the export of the erythropoietin receptor (EPOR) to cell surface, which ensures the survival and proliferation of erythroblasts. Although TFR2 has a crucial role in...
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| Veröffentlicht in: | American journal of hematology 2021-04, Vol.96 (4), p.480-492 |
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| creator | Richard, Cyrielle Viret, Sophie Cantero Aguilar, Lilia Lefevre, Carine Leduc, Marjorie Faouzi, El Hassan Azar, Nabih Lavazec, Catherine Mayeux, Patrick Verdier, Frédérique |
| description | Efficient erythropoiesis relies on the expression of the transferrin receptor type 2 (TFR2). In erythroid precursors, TFR2 facilitates the export of the erythropoietin receptor (EPOR) to cell surface, which ensures the survival and proliferation of erythroblasts. Although TFR2 has a crucial role in erythropoiesis regulation, its mechanism of action remains to be clarified. To understand its role better, we aimed at identifying its protein partners by mass‐spectrometry after immunoprecipitation in erythroid cells. Here we report the kinase MRCKα (myotonic dystrophy kinase‐related CDC42‐binding kinase α) as a new partner of both TFR2 and EPOR in erythroblasts. We show that MRCKα is co‐expressed with TFR2, and TFR1 during terminal differentiation and regulates the internalization of the two types of transferrin receptors. The knockdown of MRCKα by shRNA in human primary erythroblasts leads to a decreased cell surface expression of both TFR1 and TFR2, an increased cell‐surface expression of EPOR, and a delayed differentiation. Additionally, knockout of Mrckα in the murine MEDEP cells also leads to a striking delay in erythropoiesis, showcasing the importance of this kinase in both species. Our data highlight the importance of MRCKα in the regulation of erythropoiesis. |
| doi_str_mv | 10.1002/ajh.26104 |
| format | Article |
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In erythroid precursors, TFR2 facilitates the export of the erythropoietin receptor (EPOR) to cell surface, which ensures the survival and proliferation of erythroblasts. Although TFR2 has a crucial role in erythropoiesis regulation, its mechanism of action remains to be clarified. To understand its role better, we aimed at identifying its protein partners by mass‐spectrometry after immunoprecipitation in erythroid cells. Here we report the kinase MRCKα (myotonic dystrophy kinase‐related CDC42‐binding kinase α) as a new partner of both TFR2 and EPOR in erythroblasts. We show that MRCKα is co‐expressed with TFR2, and TFR1 during terminal differentiation and regulates the internalization of the two types of transferrin receptors. The knockdown of MRCKα by shRNA in human primary erythroblasts leads to a decreased cell surface expression of both TFR1 and TFR2, an increased cell‐surface expression of EPOR, and a delayed differentiation. Additionally, knockout of Mrckα in the murine MEDEP cells also leads to a striking delay in erythropoiesis, showcasing the importance of this kinase in both species. Our data highlight the importance of MRCKα in the regulation of erythropoiesis.</description><identifier>ISSN: 0361-8609</identifier><identifier>EISSN: 1096-8652</identifier><identifier>DOI: 10.1002/ajh.26104</identifier><identifier>PMID: 33476437</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Animals ; cdc42 GTP-Binding Protein - metabolism ; Cdc42 protein ; Cell surface ; Cells, Cultured ; CRISPR-Cas Systems ; Endocytosis ; Erythroblasts ; Erythroblasts - cytology ; Erythroblasts - metabolism ; Erythroid cells ; Erythropoiesis ; Erythropoiesis - physiology ; Erythropoietin ; Gene Knockout Techniques ; Hematology ; Human health and pathology ; Humans ; Immunoprecipitation ; Internalization ; Iron - metabolism ; Life Sciences ; Mice ; Myotonic dystrophy ; Myotonin-Protein Kinase - isolation & purification ; Myotonin-Protein Kinase - physiology ; Receptors, Erythropoietin - metabolism ; Receptors, Transferrin - metabolism ; RNA Interference ; RNA, Small Interfering - genetics ; RNA, Small Interfering - pharmacology ; Transferrin receptors ; Transferrins</subject><ispartof>American journal of hematology, 2021-04, Vol.96 (4), p.480-492</ispartof><rights>2021 Wiley Periodicals LLC.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4224-21b7a3f282c26b561028ada0fb12085c6534acaf9fb10856ae2228479bf7206f3</citedby><cites>FETCH-LOGICAL-c4224-21b7a3f282c26b561028ada0fb12085c6534acaf9fb10856ae2228479bf7206f3</cites><orcidid>0000-0001-7267-0298 ; 0000-0003-1533-7282 ; 0000-0002-4049-3976</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fajh.26104$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fajh.26104$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33476437$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03400346$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Richard, Cyrielle</creatorcontrib><creatorcontrib>Viret, Sophie</creatorcontrib><creatorcontrib>Cantero Aguilar, Lilia</creatorcontrib><creatorcontrib>Lefevre, Carine</creatorcontrib><creatorcontrib>Leduc, Marjorie</creatorcontrib><creatorcontrib>Faouzi, El Hassan</creatorcontrib><creatorcontrib>Azar, Nabih</creatorcontrib><creatorcontrib>Lavazec, Catherine</creatorcontrib><creatorcontrib>Mayeux, Patrick</creatorcontrib><creatorcontrib>Verdier, Frédérique</creatorcontrib><title>Myotonic dystrophy kinase‐related CDC42‐binding kinase α, a new transferrin receptor type 2‐binding partner, is a regulator of erythropoiesis</title><title>American journal of hematology</title><addtitle>Am J Hematol</addtitle><description>Efficient erythropoiesis relies on the expression of the transferrin receptor type 2 (TFR2). In erythroid precursors, TFR2 facilitates the export of the erythropoietin receptor (EPOR) to cell surface, which ensures the survival and proliferation of erythroblasts. Although TFR2 has a crucial role in erythropoiesis regulation, its mechanism of action remains to be clarified. To understand its role better, we aimed at identifying its protein partners by mass‐spectrometry after immunoprecipitation in erythroid cells. Here we report the kinase MRCKα (myotonic dystrophy kinase‐related CDC42‐binding kinase α) as a new partner of both TFR2 and EPOR in erythroblasts. We show that MRCKα is co‐expressed with TFR2, and TFR1 during terminal differentiation and regulates the internalization of the two types of transferrin receptors. The knockdown of MRCKα by shRNA in human primary erythroblasts leads to a decreased cell surface expression of both TFR1 and TFR2, an increased cell‐surface expression of EPOR, and a delayed differentiation. Additionally, knockout of Mrckα in the murine MEDEP cells also leads to a striking delay in erythropoiesis, showcasing the importance of this kinase in both species. 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Viret, Sophie ; Cantero Aguilar, Lilia ; Lefevre, Carine ; Leduc, Marjorie ; Faouzi, El Hassan ; Azar, Nabih ; Lavazec, Catherine ; Mayeux, Patrick ; Verdier, Frédérique</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4224-21b7a3f282c26b561028ada0fb12085c6534acaf9fb10856ae2228479bf7206f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>cdc42 GTP-Binding Protein - metabolism</topic><topic>Cdc42 protein</topic><topic>Cell surface</topic><topic>Cells, Cultured</topic><topic>CRISPR-Cas Systems</topic><topic>Endocytosis</topic><topic>Erythroblasts</topic><topic>Erythroblasts - cytology</topic><topic>Erythroblasts - metabolism</topic><topic>Erythroid cells</topic><topic>Erythropoiesis</topic><topic>Erythropoiesis - physiology</topic><topic>Erythropoietin</topic><topic>Gene Knockout Techniques</topic><topic>Hematology</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Immunoprecipitation</topic><topic>Internalization</topic><topic>Iron - metabolism</topic><topic>Life Sciences</topic><topic>Mice</topic><topic>Myotonic dystrophy</topic><topic>Myotonin-Protein Kinase - isolation & purification</topic><topic>Myotonin-Protein Kinase - physiology</topic><topic>Receptors, Erythropoietin - metabolism</topic><topic>Receptors, Transferrin - metabolism</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>Transferrin receptors</topic><topic>Transferrins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Richard, Cyrielle</creatorcontrib><creatorcontrib>Viret, Sophie</creatorcontrib><creatorcontrib>Cantero Aguilar, Lilia</creatorcontrib><creatorcontrib>Lefevre, Carine</creatorcontrib><creatorcontrib>Leduc, Marjorie</creatorcontrib><creatorcontrib>Faouzi, El Hassan</creatorcontrib><creatorcontrib>Azar, Nabih</creatorcontrib><creatorcontrib>Lavazec, Catherine</creatorcontrib><creatorcontrib>Mayeux, Patrick</creatorcontrib><creatorcontrib>Verdier, Frédérique</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>American journal of hematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Richard, Cyrielle</au><au>Viret, Sophie</au><au>Cantero Aguilar, Lilia</au><au>Lefevre, Carine</au><au>Leduc, Marjorie</au><au>Faouzi, El Hassan</au><au>Azar, Nabih</au><au>Lavazec, Catherine</au><au>Mayeux, Patrick</au><au>Verdier, Frédérique</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Myotonic dystrophy kinase‐related CDC42‐binding kinase α, a new transferrin receptor type 2‐binding partner, is a regulator of erythropoiesis</atitle><jtitle>American journal of hematology</jtitle><addtitle>Am J Hematol</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>96</volume><issue>4</issue><spage>480</spage><epage>492</epage><pages>480-492</pages><issn>0361-8609</issn><eissn>1096-8652</eissn><abstract>Efficient erythropoiesis relies on the expression of the transferrin receptor type 2 (TFR2). In erythroid precursors, TFR2 facilitates the export of the erythropoietin receptor (EPOR) to cell surface, which ensures the survival and proliferation of erythroblasts. Although TFR2 has a crucial role in erythropoiesis regulation, its mechanism of action remains to be clarified. To understand its role better, we aimed at identifying its protein partners by mass‐spectrometry after immunoprecipitation in erythroid cells. Here we report the kinase MRCKα (myotonic dystrophy kinase‐related CDC42‐binding kinase α) as a new partner of both TFR2 and EPOR in erythroblasts. We show that MRCKα is co‐expressed with TFR2, and TFR1 during terminal differentiation and regulates the internalization of the two types of transferrin receptors. The knockdown of MRCKα by shRNA in human primary erythroblasts leads to a decreased cell surface expression of both TFR1 and TFR2, an increased cell‐surface expression of EPOR, and a delayed differentiation. Additionally, knockout of Mrckα in the murine MEDEP cells also leads to a striking delay in erythropoiesis, showcasing the importance of this kinase in both species. Our data highlight the importance of MRCKα in the regulation of erythropoiesis.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>33476437</pmid><doi>10.1002/ajh.26104</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-7267-0298</orcidid><orcidid>https://orcid.org/0000-0003-1533-7282</orcidid><orcidid>https://orcid.org/0000-0002-4049-3976</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0361-8609 |
| ispartof | American journal of hematology, 2021-04, Vol.96 (4), p.480-492 |
| issn | 0361-8609 1096-8652 |
| language | eng |
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| source | MEDLINE; Access via Wiley Online Library; EZB-FREE-00999 freely available EZB journals; Wiley Online Library (Open Access Collection) |
| subjects | Animals cdc42 GTP-Binding Protein - metabolism Cdc42 protein Cell surface Cells, Cultured CRISPR-Cas Systems Endocytosis Erythroblasts Erythroblasts - cytology Erythroblasts - metabolism Erythroid cells Erythropoiesis Erythropoiesis - physiology Erythropoietin Gene Knockout Techniques Hematology Human health and pathology Humans Immunoprecipitation Internalization Iron - metabolism Life Sciences Mice Myotonic dystrophy Myotonin-Protein Kinase - isolation & purification Myotonin-Protein Kinase - physiology Receptors, Erythropoietin - metabolism Receptors, Transferrin - metabolism RNA Interference RNA, Small Interfering - genetics RNA, Small Interfering - pharmacology Transferrin receptors Transferrins |
| title | Myotonic dystrophy kinase‐related CDC42‐binding kinase α, a new transferrin receptor type 2‐binding partner, is a regulator of erythropoiesis |
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