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ELKS1 controls mast cell degranulation by regulating the transcription of Stxbp2 and Syntaxin 4 via Kdm2b stabilization.


ABSTRACT: ELKS1 is a protein with proposed roles in regulated exocytosis in neurons and nuclear factor ?B (NF-?B) signaling in cancer cells. However, how these two potential roles come together under physiological settings remain unknown. Since both regulated exocytosis and NF-?B signaling are determinants of mast cell (MC) functions, we generated mice lacking ELKS1 in connective tissue MCs (Elks1f/f Mcpt5-Cre) and found that while ELKS1 is dispensable for NF-?B-mediated cytokine production, it is essential for MC degranulation both in vivo and in vitro. Impaired degranulation was caused by reduced transcription of Syntaxin 4 (STX4) and Syntaxin binding protein 2 (Stxpb2), resulting from a lack of ELKS1-mediated stabilization of lysine-specific demethylase 2B (Kdm2b), which is an essential regulator of STX4 and Stxbp2 transcription. These results suggest a transcriptional role for active-zone proteins like ELKS1 and suggest that they may regulate exocytosis through a novel mechanism involving transcription of key exocytosis proteins.

SUBMITTER: Lam HY 

PROVIDER: S-EPMC7531903 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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ELKS1 controls mast cell degranulation by regulating the transcription of Stxbp2 and Syntaxin 4 via Kdm2b stabilization.

Lam Hiu Yan HY   Arumugam Surendar S   Bae Han Gyu HG   Wang Cheng Chun CC   Jung Sangyong S   St John Ashley Lauren AL   Hong Wanjin W   Han Weiping W   Tergaonkar Vinay V  

Science advances 20200731 31


ELKS1 is a protein with proposed roles in regulated exocytosis in neurons and nuclear factor κB (NF-κB) signaling in cancer cells. However, how these two potential roles come together under physiological settings remain unknown. Since both regulated exocytosis and NF-κB signaling are determinants of mast cell (MC) functions, we generated mice lacking ELKS1 in connective tissue MCs (<i>Elks1<sup>f/f</sup> Mcpt5</i>-Cre) and found that while ELKS1 is dispensable for NF-κB-mediated cytokine product  ...[more]

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