Functional requirements for a Samd14-capping protein complex in stress erythropoiesis
- University of Nebraska Medical Center, United States
- University of Nebraska-Lincoln, United States
Abstract
Acute anemia induces rapid expansion of erythroid precursors and accelerated differentiation to replenish erythrocytes. Paracrine signals involving cooperation between SCF/Kit signaling and other signaling inputs are required for the increased erythroid precursor activity in anemia. Our prior work revealed that the Sterile Alpha Motif (SAM) Domain 14 (Samd14) gene increases the regenerative capacity of the erythroid system in a mouse genetic model and promotes stress-dependent Kit signaling. However, the mechanism underlying Samd14's role in stress erythropoiesis is unknown. We identified a protein-protein interaction between Samd14 and the α- and β heterodimers of the F-actin capping protein (CP) complex. Knockdown of the CP β subunit increased erythroid maturation in murine ex vivo cultures and decreased colony forming potential of stress erythroid precursors. In a genetic complementation assay for Samd14 activity, our results revealed that the Samd14-CP interaction is a determinant of erythroid precursor cell levels and function. Samd14-CP promotes SCF/Kit signaling in CD71med spleen erythroid precursors. Given the roles of Kit signaling in hematopoiesis and Samd14 in Kit pathway activation, this mechanism may have pathological implications in acute/chronic anemia.
Data availability
The mass spectrometry proteomics data was deposited to the ProteomeXchange Consortium via the PRIDE (Perez-Riverol et al, 2019) partner repository with the dataset identifier PXD030467 and 10.6019/PXD030467. All other data generated or analysed during this study are included in the manuscript and supporting file.
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Chromatin state dynamics during blood formationNCBI Gene Expression Omnibus, GSE60103.
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Author details
Funding
NHLBI Division of Intramural Research (R01 HL155439-01)
- Suhita Ray
- Linda Chee
- Yichao Zhou
- Meg A Schaefer
- Kyle Hewitt
GMS (1P20GM121316-01-A1)
- Kyle Hewitt
Nebraska Stem Cell Research (LB606)
- Suhita Ray
- Linda Chee
- Yichao Zhou
- Meg A Schaefer
- Michael J Naldrett
- Sophie Alvarez
- Nicholas T Woods
- Kyle Hewitt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#18-099-08 FC) of the University of Nebraska Medical Center.
Copyright
© 2022, Ray et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Functional requirements for a Samd14-capping protein complex in stress erythropoiesis
eLife 11:e76497.
https://doi.org/10.7554/eLife.76497
