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Proximity assay of p38alpha MAPK reveals alternative splicing regulatory mechanism in cardiomyocyte.

ABSTRACT: The mitogen-activated protein kinase (MAPK) p38 signaling pathway is essential for normal heart function. However, p38 also contributes to heart failure pathogenesis by affecting heart contractility and cardiomyocyte survival. To unravel the complex cardiac role of p38, we report the interactome of p38α and p38γ, the two well expressed isoforms in the heart, obtained via an APEX proximity assay performed in cultured neonatal rat ventricular myocytes. The p38α and p38γ have distinct interactomes in cardiomyocytes for both studied states; basal and activated by an osmotic stress. Interestingly, the activated p38α interactome contains many spliceosome implicated RNA-binding proteins. The serine/arginine-rich splicing factor 3 (SRSF3) is of particular interest and its interaction with p38α was validated by co-immunoprecipitation. p38 is sufficient to partially relocate nuclear SRSF3 to cytoplasm. The alternative splicing function of SRSF3 is also modulated by the p38 pathway. Our findings reveal a novel set of proteins to investigate in order to decipher cardiac functions of the MAPK p38, as well as a specific regulation mechanism of SRSF3 by p38 in cardiomyocytes.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Heart, Primary Cell, Cell Culture

SUBMITTER: Mannix Auger-Messier

LAB HEAD: Mannix Auger-Messier

PROVIDER: PXD011089 | Pride | 2021-03-01

REPOSITORIES: Pride

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p38α MAPK proximity assay reveals a regulatory mechanism of alternative splicing in cardiomyocytes.

Dumont Audrey-Ann AA Dumont Lauralyne L Berthiaume Jonathan J Auger-Messier Mannix M

Biochimica et biophysica acta. Molecular cell research 20190907 12

The p38 mitogen-activated protein kinase (MAPK) signaling pathway is essential for normal heart function. However, p38 also contributes to heart failure pathogenesis by affecting cardiomyocytes contractility and survival. To unravel part of the complex role of p38 in cardiac function, we performed an APEX2-based proximity assay in cultured neonatal rat ventricular myocytes and identified the protein interaction networks (interactomes) of two highly expressed p38 isoforms in the heart. We found t ...[more]

PMID: 31505169

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	286MannixA_APEX.raw	Raw
	286MannixA_APEX_SOR.raw	Raw
	286MannixA_Alpha.raw	Raw
	286MannixA_Alpha_SOR.raw	Raw
	286MannixA_Gamma.raw	Raw