Charting the\nDynamic Trophoblast Plasma Membrane Identifies\nLYN As a Functional Regulator of Syncytialization

The differentiation of placental cytotrophoblasts (CTBs)\ninto the\nsyncytiotrophoblast (STB) layer results in a significant remodeling\nof the plasma membrane proteome. Here, we use a peroxidase-catalyzed\nproximity labeling strategy to map the dynamic plasma membrane proteomes\nof CTBs and STBs. Coupled with mass-spectrometry-based proteomics,\nwe identify hundreds of plasma membrane proteins and observe relative\nchanges in protein abundance throughout differentiation, including\nthe upregulation of the plasma-membrane-localized nonreceptor tyrosine\nkinase LYN. We show that both siRNA-mediated knockdown and small molecule\ninhibition of LYN kinase function impairs CTB fusion and reduces the\nexpression of syncytialization markers, presenting a function for\nLYN outside of its canonical role in immunological signaling. Our\nresults demonstrate the use of the proximity labeling platform to\ndiscover functional regulators within the plasma membrane and provide\nnew avenues to regulate trophoblast differentiation.