L1
神经细胞粘附分子
细胞生物学
神经突
细胞粘附
蛋白质组
细胞粘附分子
免疫球蛋白超家族
化学
生物
神经科学
细胞
生物化学
体外
基因
作者
Pamela N. Gallo,Elaine M. Mihelc,Robyn J. Eisert,Gary A. Bradshaw,Florian Dimek,Andreas Leffler,Marian Kalocsay,Vera Y. Moiseenkova‐Bell
出处
期刊:Cell Calcium
[Elsevier]
日期:2024-05-01
卷期号:: 102894-102894
标识
DOI:10.1016/j.ceca.2024.102894
摘要
TRPV2 voltage-insensitive, calcium-permeable ion channels play important roles in cancer progression, immune response, and neuronal development. Despite TRPV2's physiological impact, underlying endogenous proteins mediating TRPV2 responses and affected signaling pathways remain elusive. Using quantitative peroxidase-catalyzed (APEX2) proximity proteomics we uncover dynamic changes in the TRPV2-proximal proteome and identify calcium signaling and cell adhesion factors recruited to the molecular channel neighborhood in response to activation. Quantitative TRPV2 proximity proteomics further revealed activation-induced enrichment of protein clusters with biological functions in neural and cellular projection. We demonstrate a functional connection between TRPV2 and the neural immunoglobulin cell adhesion molecules NCAM and L1CAM. NCAM and L1CAM stimulation robustly induces TRPV2 [Ca2+]I flux in neuronal PC12 cells and this TRPV2-specific [Ca2+]I flux requires activation of the protein kinase PKCα. TRPV2 expression directly impacts neurite lengths that are modulated by NCAM or L1CAM stimulation. Hence, TRPV2's calcium signaling plays a previously undescribed, yet vital role in cell adhesion, and TRPV2 calcium flux and neurite development are intricately linked via NCAM and L1CAM cell adhesion proteins.
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