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Abstract The final stages of mammalian erythropoiesis involve enucleation, membrane and proteome remodeling, and organelle clearance. Concomitantly, the erythroid membrane skeleton establishes a unique pseudohexagonal spectrin meshwork that is connected to the membrane through junctional complexes. The mechanism and signaling pathways involved in the coordination of these processes are unclear. The results of our study revealed an unexpected role of the membrane skeleton in the modulation of proteome remodeling and organelle clearance during the final stages of erythropoiesis. We found that diaphanous-related formin mDia2 is a master regulator of the integrity of the membrane skeleton through polymerization of actin protofilament in the junctional complex. The mDia2-deficient terminal erythroid cell contained a disorganized and rigid membrane skeleton that was ineffective in detaching the extruded nucleus. In addition, the disrupted skeleton failed to activate the endosomal sorting complex required for transport-III (ESCRT-III) complex, which led to a global defect in proteome remodeling, endolysosomal trafficking, and autophagic organelle clearance. Chmp5, a component of the ESCRT-III complex, is regulated by mDia2-dependent activation of the serum response factor and is essential for membrane remodeling and autophagosome-lysosome fusion. Mice with loss of Chmp5 in hematopoietic cells in vivo resembled the phenotypes in mDia2-knockout mice. Furthermore, overexpression of Chmp5 in mDia2-deficient hematopoietic stem and progenitor cells significantly restored terminal erythropoiesis in vivo. These findings reveal a formin-regulated signaling pathway that connects the membrane skeleton to proteome remodeling, enucleation, and organelle clearance during terminal erythropoiesis. 

Abstract In this work, the Na–K liquid alloy with a charge selective interfacial layer is developed to achieve an impressively long cycling life with small overpotential on a sodium super‐ionic conductor solid‐state electrolyte (NASICON SSE). With this unique multi‐cation system as the platform, we further propose a unique model that contains a chemical decomposition domain and a kinetic decomposition domain for the interfacial stability model. Based on this model, two charge selection mechanisms are proposed with dynamic chemical kinetic equilibrium and electrochemical kinetics as the manners of control, respectively, and both are validated by the electrochemical measurements with microscopic and spectroscopic characterizations. This study provides an effective design for high‐energy‐density solid‐state battery with alkali Na–K anode, but also presents a novel approach to understand the interfacial chemical processes that could inspire and guide future designs.