The Dynamic TRPV2 Ion Channel Proximity Proteome Reveals Functional Links of Calcium Flux With Cellular Adhesion Factors Ncam and L1CAM in Neurite Outgrowth

Authors

Pamela N Gallo
Elaine Mihelc
Robyn Eisert
Gary A Bradshaw
Florian Dimek
Andreas Leffler
Marian Kalocsay
Vera Moiseenkova-Bell

Publication Date

7-1-2024

Journal

Cell Calcium

DOI

10.1016/j.ceca.2024.102894

PMID

38728789

PMCID

PMC11456977

PubMedCentral® Posted Date

7-1-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

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.

Keywords

Animals, Humans, Rats, Calcium, Calcium Signaling, Cell Adhesion, Neural Cell Adhesion Molecule L1, Neural Cell Adhesion Molecules, Neurites, Neuronal Outgrowth, PC12 Cells, Protein Kinase C-alpha, Proteome, TRPV Cation Channels, CD56 Antigen, APEX, proximity proteomics, TRPV2, neurite outgrowth, NCAM, L1CAM

Published Open-Access

yes

Recommended Citation

Gallo, Pamela N; Mihelc, Elaine; Eisert, Robyn; et al., "The Dynamic TRPV2 Ion Channel Proximity Proteome Reveals Functional Links of Calcium Flux With Cellular Adhesion Factors Ncam and L1CAM in Neurite Outgrowth" (2024). Faculty, Staff and Student Publications. 4561.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4561