Cargando…

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

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 discove...

Descripción completa

Detalles Bibliográficos
Autores principales: Cendrowski, Jaroslaw, Kaczmarek, Marta, Mazur, Michał, Kuzmicz-Kowalska, Katarzyna, Jastrzebski, Kamil, Brewinska-Olchowik, Marta, Kominek, Agata, Piwocka, Katarzyna, Miaczynska, Marta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473771/
https://www.ncbi.nlm.nih.gov/pubmed/32795391
http://dx.doi.org/10.7554/eLife.58504
_version_ 1783579234973777920
author Cendrowski, Jaroslaw
Kaczmarek, Marta
Mazur, Michał
Kuzmicz-Kowalska, Katarzyna
Jastrzebski, Kamil
Brewinska-Olchowik, Marta
Kominek, Agata
Piwocka, Katarzyna
Miaczynska, Marta
author_facet Cendrowski, Jaroslaw
Kaczmarek, Marta
Mazur, Michał
Kuzmicz-Kowalska, Katarzyna
Jastrzebski, Kamil
Brewinska-Olchowik, Marta
Kominek, Agata
Piwocka, Katarzyna
Miaczynska, Marta
author_sort Cendrowski, Jaroslaw
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7473771
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-74737712020-09-08 Splicing variation of BMP2K balances abundance of COPII assemblies and autophagic degradation in erythroid cells Cendrowski, Jaroslaw Kaczmarek, Marta Mazur, Michał Kuzmicz-Kowalska, Katarzyna Jastrzebski, Kamil Brewinska-Olchowik, Marta Kominek, Agata Piwocka, Katarzyna Miaczynska, Marta eLife Cell Biology 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. eLife Sciences Publications, Ltd 2020-08-14 /pmc/articles/PMC7473771/ /pubmed/32795391 http://dx.doi.org/10.7554/eLife.58504 Text en © 2020, Cendrowski et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Cendrowski, Jaroslaw
Kaczmarek, Marta
Mazur, Michał
Kuzmicz-Kowalska, Katarzyna
Jastrzebski, Kamil
Brewinska-Olchowik, Marta
Kominek, Agata
Piwocka, Katarzyna
Miaczynska, Marta
Splicing variation of BMP2K balances abundance of COPII assemblies and autophagic degradation in erythroid cells
title Splicing variation of BMP2K balances abundance of COPII assemblies and autophagic degradation in erythroid cells
title_full Splicing variation of BMP2K balances abundance of COPII assemblies and autophagic degradation in erythroid cells
title_fullStr Splicing variation of BMP2K balances abundance of COPII assemblies and autophagic degradation in erythroid cells
title_full_unstemmed Splicing variation of BMP2K balances abundance of COPII assemblies and autophagic degradation in erythroid cells
title_short Splicing variation of BMP2K balances abundance of COPII assemblies and autophagic degradation in erythroid cells
title_sort splicing variation of bmp2k balances abundance of copii assemblies and autophagic degradation in erythroid cells
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473771/
https://www.ncbi.nlm.nih.gov/pubmed/32795391
http://dx.doi.org/10.7554/eLife.58504
work_keys_str_mv AT cendrowskijaroslaw splicingvariationofbmp2kbalancesabundanceofcopiiassembliesandautophagicdegradationinerythroidcells
AT kaczmarekmarta splicingvariationofbmp2kbalancesabundanceofcopiiassembliesandautophagicdegradationinerythroidcells
AT mazurmichał splicingvariationofbmp2kbalancesabundanceofcopiiassembliesandautophagicdegradationinerythroidcells
AT kuzmiczkowalskakatarzyna splicingvariationofbmp2kbalancesabundanceofcopiiassembliesandautophagicdegradationinerythroidcells
AT jastrzebskikamil splicingvariationofbmp2kbalancesabundanceofcopiiassembliesandautophagicdegradationinerythroidcells
AT brewinskaolchowikmarta splicingvariationofbmp2kbalancesabundanceofcopiiassembliesandautophagicdegradationinerythroidcells
AT kominekagata splicingvariationofbmp2kbalancesabundanceofcopiiassembliesandautophagicdegradationinerythroidcells
AT piwockakatarzyna splicingvariationofbmp2kbalancesabundanceofcopiiassembliesandautophagicdegradationinerythroidcells
AT miaczynskamarta splicingvariationofbmp2kbalancesabundanceofcopiiassembliesandautophagicdegradationinerythroidcells