Photoproximity Labeling of Sialylated Glycoproteins (GlycoMap) Reveals Sialylation-Dependent Regulation of Ion Transport

Sialylation, the addition of sialic acid to glycans,
is a crucial
post-translational modification of proteins, contributing to neurodevelopment,
oncogenesis, and immune response. In cancer, sialylation is dramatically
upregulated. Yet, the functional biochemical consequences of sialylation
remain mysterious. Here, we establish a μMap proximity labeling
platform that utilizes metabolically inserted azidosialic acid to
introduce iridium-based photocatalysts on sialylated cell–surface
glycoproteins as a means to profile local microenvironments across
the sialylated proteome. In comparative experiments between primary
cervical cells and a cancerous cell line (HeLa), we identify key differences
in both the global sialome and proximal proteins, including solute
carrier proteins that regulate metabolite and ion transport. In particular,
we show that cell–surface interactions between receptors trafficking
ethanolamine and zinc are sialylation-dependent and impact intracellular
metabolite levels. These results establish a μMap method for
interrogating proteoglycan function and support a role for sialylated
glycoproteins in regulating cell–surface transporters.