Receptor-proximal phosphoform organization precedes β2 integrin activation

Recent studies have challenged the traditional view of receptor signaling as a process of protein recruitment following stimulation. A new research paper delves into the pre-existing molecular organization of receptor signaling, focusing specifically on the β2 integrins on leukocytes. By employing CD18-APEX2 proximity labeling and a spatial membrane reference, scientists quantified the proteins and phosphosites near these integrins.

Under resting conditions, the receptors, adaptors, and Rap GTPases were predominantly represented compared to several catalytic classes. The researchers then performed a parent-protein correction to reveal spatial phosphoform organization. They discovered that 32% of the 4,564 phosphosites deviated significantly from the distribution center, while 56% of the proteins with multiple quantified sites showed divergence beyond measurement error.

When the researchers examined the effects of sustained activation, 31% of the phosphosites were altered, while 95.9% of the proteins remained equivalent, within ±0.5 log2. Remarkably, the spatial phosphoform organization largely persisted during these changes.

The majority of phosphorylation responses were shared across both labeling environments. However, receptor-preferential changes were dominated by phosphosites. The authors conclude that receptor signaling can regulate pre-existing molecular states without necessitating extensive protein redistribution.