Surface delivery quantification reveals distinct trafficking efficiencies among clustered protocadherin isoforms

• 成果类型: Article
• 署名作者: May, Elizabeth J.; Gaudet, Rachelle
• 署名单位: Harvard University; University of California System; University of California Berkeley
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12878
• DOI: 10.1073/pnas.2514178122
• 发表日期: 2025-08-05
• 关键词: gamma-protocadherins; cytoplasmic domain; homophilic interactions; alpha-protocadherins; structural basis; large family; sequence; RECOGNITION; expression; diversity

摘要

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.