Mapping of\nβ3-Adrenergic Receptor in Living\nCells with a Ligand-Guided Fluorescent Probe

Tracking the dynamic distribution of native proteins\nin living\ncells or tissues in real time is essential for understanding the functional\nmechanisms involved in their physiological or pathological processes.\nThe β3-adrenergic receptor (β3-AR) has important biological\nfunctions. It is expected to be a diagnostic indicator for aging,\nyet current probes for β-ARs are unable to dynamically monitor\nβ3-AR in real time, which impedes the progress of β3-AR\nresearch. Here, we developed a ligand-directed anchoring probe, <b>β3-ARP</b>, that precisely covalently anchors with native\nβ3-AR in living cells, for the diagnosis of senescence. The\nligand-directed anchoring probe selectively recognizes and traces\nβ3-AR and can achieve dynamic observation and monitoring of\nβ3-AR in living cells, including the interaction between lipid\ndroplets and mitochondria. Moreover, we were able to directly probe\nthe distribution of β3-AR in various organs of aging mice in\nsitu and track the location of native β3-AR in different types\nof primary neuronal cells using <b>β3-ARP</b> and two-photon\nimaging, which revealed the aberrant accumulation of lipid droplets\nand the distribution of β3-AR in neurological diseases. This\nresearch has resulted in a new covalently anchoring fluorescent probe, <b>β3-ARP</b>, which could serve as a powerful tool to explore\nthe link between β3-AR and age-related diseases.