Journal
SCIENCE ADVANCES
Volume 6, Issue 31, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abb2497
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Funding
- Singapore National Research Foundation [NRF-CRP17-2017-02]
- Joint Council Office grant [BMSI/15-800003-SBIC-00E]
- Agency for Science, Technology and Research, Singapore (A*STAR)
- SINGA scholarship from A*STAR
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ELKS1 is a protein with proposed roles in regulated exocytosis in neurons and nuclear factor kappa B (NF-kappa B) signaling in cancer cells. However, how these two potential roles come together under physiological settings remain unknown. Since both regulated exocytosis and NF-kappa B signaling are determinants of mast cell (MC) functions, we generated mice lacking ELKS1 in connective tissue MCs (Elks 1(f/f) Mcpt5-Cre) and found that while ELKS1 is dispensable for NF-kappa 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.
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