Tess C Branon

Abstract Secreted proteins regulate many aspects of animal biology and are attractive targets for biomarkers and therapeutics. However, comprehensively identifying the “secretome”, along with their tissues of origin, remains extremely challenging. To address this, we employed multiple ‘omics methods to define a tissue-secretome map of 535 blood plasma proteins derived from specific cell-types and organs in Drosophila melanogaster.

Abstract Hedgehog (Hh) signaling relies on the primary cilium, a cell surface organelle that serves as a signaling hub for the cell. Using proximity labeling and quantitative proteomics, we identify Numb as a ciliary protein that positively regulates Hh signaling. Numb localizes to the ciliary pocket and acts as an endocytic adaptor to incorporate Ptch1 into clathrin-coated vesicles, thereby promoting Ptch1 exit from the cilium, a key step in Hh signaling activation.

Highlights • Proximity labeling in living C. elegans identifies ncMTOC proteins • WDR-62, VAB-10B, and actin filaments drive ncMTOC function and assembly • Functionally distinct ncMTOC modules control microtubule growth and localization • The apical ncMTOC is physically and functionally distinct from the centrosome Summary Microtubules are polarized intracellular polymers that play key roles in the cell, including in transport, polarity, and cell division.