Splicing variation of BMP2K balances abundance of COPII assemblies and autophagic degradation in erythroid cells
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.
Data availability
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD013542
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Funding
Narodowe Centrum Nauki (UMO-2011/02/A/NZ3/00149)
- Jaroslaw Cendrowski
- Katarzyna Kuzmicz-Kowalska
- Kamil Jastrzebski
- Marta Miaczynska
Fundacja na rzecz Nauki Polskiej (POIR.04.04.00-00-20CE/16-00)
- Marta Kaczmarek
- Kamil Jastrzebski
- Marta Miaczynska
Fundacja na rzecz Nauki Polskiej (POIR.04.04.00-00-1C54/16-00)
- Jaroslaw Cendrowski
- Michał Mazur
Fundacja na rzecz Nauki Polskiej (POIR.04.04.00-00-23C2/17-00)
- Katarzyna Piwocka
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Cendrowski 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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