The dynamic TRPV2 ion channel proximity proteome reveals functional links of calcium flux with cellular adhesion factors NCAM and L1CAM in neurite outgrowth.

Autor: Gallo PN; University of Pennsylvania, Systems Pharmacology and Translational Therapeutics, Philadelphia, PA, USA., Mihelc E; University of Pennsylvania, Systems Pharmacology and Translational Therapeutics, Philadelphia, PA, USA., Eisert R; Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology, Boston, MA, USA., Bradshaw GA; Harvard Medical School, Laboratory of Systems Pharmacology, Boston, MA, USA., Dimek F; Hannover Medical School, Department of Anesthesiology and Intensive Care Medicine, Hannover, Germany., Leffler A; Hannover Medical School, Department of Anesthesiology and Intensive Care Medicine, Hannover, Germany., Kalocsay M; The University of Texas MD Anderson Cancer Center, Department of Experimental Radiation Oncology, Houston, TX, USA. Electronic address: MKalocsay@mdanderson.org., Moiseenkova-Bell V; University of Pennsylvania, Systems Pharmacology and Translational Therapeutics, Philadelphia, PA, USA. Electronic address: vmb@pennmedicine.upenn.edu.
Jazyk: angličtina
Zdroj: Cell calcium [Cell Calcium] 2024 Jul; Vol. 121, pp. 102894. Date of Electronic Publication: 2024 May 04.
DOI: 10.1016/j.ceca.2024.102894
Abstrakt: 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 [Ca 2+ ] I flux in neuronal PC12 cells and this TRPV2-specific [Ca 2+ ] 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.
Competing Interests: Declaration of competing interest The authors have no competing interests to declare.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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