Mark von Zastrow

This study uses deep mutational pharmacology to show how different residues in the -opioid receptor determine the efficacy of opioids by shaping distinct activation mechanisms.

The paper shows that primary cilia in striatal neurons facilitate dopamine receptor-initiated cAMP/PKA signaling beyond the cilium, challenging the view that ciliary neurotransmission is restricted to non-canonical pathways.

The paper shows that GPCRs can distinguish neuromodulatory inputs through temporal coding, despite sharing a common transducer pathway.

This study investigates how GPCRs regulate G protein activity on endosomes using conformational biosensors, finding that endocytosis is required for active Gs production on endosomes.

This paper develops an engineered nanobody inhibitor to control opioid receptor function with subcellular precision and demonstrates its effectiveness in vivo.

This study shows GPR88 localizes to primary cilia in specific neuronal cell types in the striatum and somatosensory cortex.

This study shows that the mu-opioid receptor increases endosomal G protein activity without requiring receptor internalization or endosomal activation.

The paper shows that endocytosis differentiates cAMP signaling profiles of co-expressed GPCRs by shaping spatiotemporal cAMP dynamics.

This paper introduces a scalable proximity proteomics pipeline that improves reproducibility and throughput in biotinylation-based spatial proteomics.

This paper identifies endocytic trafficking as a mechanism for presynaptic opioid tolerance, showing that receptor cycling and phosphorylation-dependent endocytosis contribute to tolerance development.

The paper identifies novel regulators of mu opioid receptor signaling and trafficking using proximity labeling and proteomics.

This study develops a biosensor to map opioid receptor activation in neurons, showing drugs activate receptors in the Golgi and dendrites, while peptides activate them in the plasma membrane and endosomes.