Lam, H. Y., Arumugam, S., Bae, H. G., Wang, C. C., Jung, S., St. John, A. L., … Tergaonkar, V. (2020). ELKS1 controls mast cell degranulation by regulating the transcription of Stxbp2 and Syntaxin 4 via Kdm2b stabilization. Science Advances, 6(31), eabb2497. doi:10.1126/sciadv.abb2497
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 (Elks1f/f Mcpt5-Cre) and found that while ELKS1 is dispensable for NF-κB–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.
Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
This research / project is supported by the Singapore National Research Foundation - Competitive Research Programme
Grant Reference no. : NRF-CRP17-2017-02
This research / project is supported by the Agency for Science, Technology and Research, Singapore (A*STAR) - Joint Council Office grant
Grant Reference no. : BMSI/15-800003-SBIC-00E