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  • Splicing variation of BMP2K balances abundance of COPII assemblies and autophagic degradation in erythroid cells.

Splicing variation of BMP2K balances abundance of COPII assemblies and autophagic degradation in erythroid cells.

eLife (2020-08-17)
Jaroslaw Cendrowski, Marta Kaczmarek, Michał Mazur, Katarzyna Kuzmicz-Kowalska, Kamil Jastrzebski, Marta Brewinska-Olchowik, Agata Kominek, Katarzyna Piwocka, Marta Miaczynska
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MISSION® esiRNA, targeting human BMP2K
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Bafilomycin A1 from Streptomyces griseus, ≥90% (HPLC)
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Monoclonal Anti-α-Tubulin antibody produced in mouse, ascites fluid, clone B-5-1-2
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Benzidine dihydrochloride, ≥99% (titration)
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Phosphatase Inhibitor Cocktail 3, DMSO solution
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Hemin, from bovine, ≥90%
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holo-Transferrin human, powder, BioReagent, suitable for cell culture, ≥97%
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Monoclonal Anti-Vinculin antibody produced in mouse, clone hVIN-1, ascites fluid
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Phosphatase Inhibitor Cocktail 2, aqueous solution (dark coloration may develop upon storage, which does not affect the activity)
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Insulin human, recombinant, expressed in yeast, γ-irradiated, suitable for cell culture