Surface delivery quantification reveals distinct trafficking efficiencies among clustered protocadherin isoforms.

ABSTRACT: Proteins that transmit molecules and signals across the plasma membrane are crucial in cell biology because they enable cells to sense and respond to their surroundings. A major challenge for studying cell surface proteins is that often they do not fold or traffic properly to the plasma membrane when produced in heterologous cells. We developed a strategy for quantifying surface localization from fluorescence microscopy images of surface-stained cells. Using clustered protocadherins, a protein family important for cell-cell recognition during neuronal development, we found that surface delivery levels vary among clustered protocadherin isoforms and between wild-type and engineered variants. Quantifying these differences provides evidence that cis dimerization is not tightly coupled to surface delivery for clustered protocadherins. This work establishes a generalizable framework for screening proteins and variants of interest for proper cell surface localization.

SUBMITTER: May EJ 

PROVIDER: S-EPMC12337331 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature