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

Authors

Suhita Ray, University of Nebraska Medical Center
Linda Chee, University of Nebraska Medical CenterFollow
Yichao Zhou, University of Nebraska Medical Center
Meg A. Schaefer, University of Nebraska Medical Center
Michael J. Naldrett, University of Nebraska - LincolnFollow
Sophie Alvarez, University of Nebraska-Lincoln
Nicholas T. Woods, University of Nebraska Medical CenterFollow
Kyle J. Hewitt, University of Nebraska Medical CenterFollow

Document Type

Article

Date of this Version

6-17-2022

Citation

Ray et al. eLife 2022;11:e76497. DOI: https://doi.org/10.7554/eLife.76497

Comments

Copyright Ray et al. This article is distributed under the terms of the Creative Commons Attribution License,

Abstract

Acute anemia induces rapid expansion of erythroid precursors and accelerated differentiation to replenish erythrocytes. Paracrine signals—involving cooperation between stem cell factor (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.