Functional requirements for a Samd14-capping protein complex in stress erythropoiesis

  1. Suhita Ray
  2. Linda Chee
  3. Yichao Zhou
  4. Meg A Schaefer
  5. Michael J Naldrett
  6. Sophie Alvarez
  7. Nicholas T Woods
  8. Kyle Hewitt  Is a corresponding author
  1. University of Nebraska Medical Center, United States
  2. 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.

The following previously published data sets were used

Article and author information

Author details

  1. Suhita Ray

    Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0887-6640
  2. Linda Chee

    Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yichao Zhou

    Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Meg A Schaefer

    Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Michael J Naldrett

    Proteomics and Metabolomics Facility, University of Nebraska-Lincoln, Lincoln, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Sophie Alvarez

    Proteomics and Metabolomics Facility, University of Nebraska-Lincoln, Lincoln, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Nicholas T Woods

    Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Kyle Hewitt

    Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, United States
    For correspondence
    kyle.hewitt@unmc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1946-625X

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.

Reviewing Editor

  1. Jian Xu, University of Texas Southwestern Medical Center, United States

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.

Version history

  1. Received: December 17, 2021
  2. Preprint posted: January 1, 2022 (view preprint)
  3. Accepted: June 6, 2022
  4. Accepted Manuscript published: June 17, 2022 (version 1)
  5. Version of Record published: July 14, 2022 (version 2)

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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  1. Suhita Ray
  2. Linda Chee
  3. Yichao Zhou
  4. Meg A Schaefer
  5. Michael J Naldrett
  6. Sophie Alvarez
  7. Nicholas T Woods
  8. Kyle Hewitt
(2022)
Functional requirements for a Samd14-capping protein complex in stress erythropoiesis
eLife 11:e76497.
https://doi.org/10.7554/eLife.76497

Share this article

https://doi.org/10.7554/eLife.76497

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