NRas Nanoclusters Mediate Crosstalk Between BRAF/ERK and PI3K/AKT Signaling in Melanoma Cells.

ABSTRACT: Melanocyte signaling through the MAPK pathway is orchestrated by NRas and relayed downstream via multiple effectors, such as RAF, Ral, and PI3K. In spite of their significance, the molecular mechanisms of signaling relay by NRas, their dynamics, and their potential as therapeutic targets remain unclear. Using multi-color single molecule localization microscopy (PALM and dSTORM), we resolved the mutual nanoscale organization of NRas, PI3K, and BRAF at the plasma membrane of fixed and live melanoma cells. Surprisingly, NRas and its oncogenic mutation Q61R colocalized with PI3K in mutual nanoclusters, where BRAF was also frequently present. In live cells, NRas and PI3K co-clustering declined, yet persisted over minutes. Clinically relevant perturbations revealed unexpected crosstalk within th

SUBMITTER: Yakovian O 

PROVIDER: S-EPMC12692423 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature