Laboratory of Cell Biology, International Institute of Molecular and Cell Biology, Warsaw, Poland.
Laboratory of Cytometry, Nencki Institute of Experimental Biology, Warsaw, Poland.
Elife. 2020 Aug 14;9:e58504. doi: 10.7554/eLife.58504.
Intracellular transport undergoes remodeling upon cell differentiation, which involves cell type-specific regulators. Bone morphogenetic protein 2-inducible kinase (BMP2K) has been potentially implicated in endocytosis and cell differentiation but its molecular functions remained unknown. We discovered that its longer (L) and shorter (S) splicing variants regulate erythroid differentiation in a manner unexplainable by their involvement in AP-2 adaptor phosphorylation and endocytosis. However, both variants interact with SEC16A and could localize to the juxtanuclear secretory compartment. Variant-specific depletion approach showed that BMP2K isoforms constitute a BMP2K-L/S regulatory system that controls the distribution of SEC16A and SEC24B as well as SEC31A abundance at COPII assemblies. Finally, we found L to promote and S to restrict autophagic degradation and erythroid differentiation. Hence, we propose that BMP2K-L and BMP2K-S differentially regulate abundance and distribution of COPII assemblies as well as autophagy, possibly thereby fine-tuning erythroid differentiation.
细胞内运输在细胞分化时会发生重构，涉及细胞类型特异性的调节因子。骨形态发生蛋白 2 诱导激酶（BMP2K）可能参与内吞作用和细胞分化，但它的分子功能尚不清楚。我们发现，其较长（L）和较短（S）剪接变体以一种无法用它们参与 AP-2 衔接蛋白磷酸化和内吞作用来解释的方式调节红细胞分化。然而，这两种变体都与 SEC16A 相互作用，并能定位于核周分泌隔室。变体特异性耗竭方法表明，BMP2K 异构体构成 BMP2K-L/S 调节系统，控制 SEC16A 和 SEC24B 的分布以及 COPII 组装处 SEC31A 的丰度。最后，我们发现 L 促进和 S 限制自噬降解和红细胞分化。因此，我们提出 BMP2K-L 和 BMP2K-S 差异调节 COPII 组装体以及自噬的丰度和分布，从而可能精细调节红细胞分化。
