Myotonic dystrophy kinase-related CDC42-binding kinase α, a new transferrin receptor type 2-binding partner, is a regulator of erythropoiesis.
Animals
CRISPR-Cas Systems
Cells, Cultured
Endocytosis
Erythroblasts
/ cytology
Erythropoiesis
/ physiology
Gene Knockout Techniques
Humans
Iron
/ metabolism
Mice
Myotonin-Protein Kinase
/ isolation & purification
RNA Interference
RNA, Small Interfering
/ genetics
Receptors, Erythropoietin
/ metabolism
Receptors, Transferrin
/ metabolism
cdc42 GTP-Binding Protein
/ metabolism
Journal
American journal of hematology
ISSN: 1096-8652
Titre abrégé: Am J Hematol
Pays: United States
ID NLM: 7610369
Informations de publication
Date de publication:
01 04 2021
01 04 2021
Historique:
received:
01
10
2020
revised:
12
01
2021
accepted:
18
01
2021
pubmed:
22
1
2021
medline:
24
4
2021
entrez:
21
1
2021
Statut:
ppublish
Résumé
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.
Substances chimiques
Cdc42 protein, mouse
0
RNA, Small Interfering
0
Receptors, Erythropoietin
0
Receptors, Transferrin
0
TFR2 protein, human
0
Iron
E1UOL152H7
CDC42BPA protein, human
EC 2.7.1.-
Myotonin-Protein Kinase
EC 2.7.11.1
CDC42 protein, human
EC 3.6.5.2
cdc42 GTP-Binding Protein
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
480-492Informations de copyright
© 2021 Wiley Periodicals LLC.
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