scholarly journals Splicing variation of BMP2K balances endocytosis, COPII trafficking and autophagy in erythroid cells

2020 ◽  
Author(s):  
Jaroslaw Cendrowski ◽  
Marta Kaczmarek ◽  
Katarzyna Kuzmicz-Kowalska ◽  
Michal Mazur ◽  
Kamil Jastrzebski ◽  
...  

ABSTRACTIntracellular 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 interacted with SEC16A whose silencing in K562 erythroid leukemia cells affected generation of COPII assemblies and induced autophagic degradation. Variant-specific depletion approach showed that BMP2K isoforms constitute a BMP2K-L/S regulatory system. Therein, L promotes while S restricts recruitment of SEC31A to SEC24B-containing COPII structures forming at SEC16A-positive ER exit sites. Finally, we found L to promote and S to restrict autophagic degradation. Hence, we propose that BMP2K-L favors SEC16A-dependent intracellular processes important for erythroid maturation, such as COPII trafficking and autophagy, in a manner inhibited by BMP2K-S.

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jaroslaw Cendrowski ◽  
Marta Kaczmarek ◽  
Michał Mazur ◽  
Katarzyna Kuzmicz-Kowalska ◽  
Kamil Jastrzebski ◽  
...  

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.


2007 ◽  
Vol 361-363 ◽  
pp. 1025-1028 ◽  
Author(s):  
Takashi Kumagai ◽  
Takahisa Anada ◽  
Yoshitomo Honda ◽  
Masamichi Takami ◽  
Ryutaro Kamijyo ◽  
...  

The present study was designed to investigate whether bone morphogenetic protein-2 (BMP-2) adsorbed onto octacalcium phosphate (OCP) and hydroxyapatite (HA) surfaces influences osteoblastic cell differentiation. Osteoblastic cell line, UAMS32, were cultured on plastic plate that was coated of synthetic OCP and HA. BMP-2 was pre-adsorbed on these calcium phosphates at 4°C or room temperature for 24h. The cells more proliferated on the BMP-2 pre-adsorbed OCP and HA than that of the controls (OCP and HA coating without BMP-2). ALP activities were higher on HA than on OCP when BMP-2 were pre-adsorbed at 4°C than at room temperature. The results suggest that pre-adsorption of BMP-2 in different temperature affects osteoblastic cell differentiation, most probably through different adsorption state of BMP-2 on this calcium phosphate.


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