M. von Zastrow

β-arrestin-independent endosomal cAMP signaling by a polypeptide hormone GPCR

This paper shows that VIPR1 can generate endosomal cAMP signals without β-arrestin, revealing β-arrestin's role in shaping the spatiotemporal profile of GPCR signaling.

Spatial organization of adenylyl cyclase and its impact on dopamine signaling in neurons

The paper investigates the spatial localization of adenylyl cyclase (AC) isoforms in striatal neurons and demonstrates how their subcellular distribution affects dopamine signaling and PKA activity.

A genome-wide CRISPR interference screen using an engineered trafficking biosensor reveals a role for RME-8 in opioid receptor regulation

The paper uses a CRISPR interference screen with a trafficking biosensor to identify genes regulating opioid receptor trafficking, finding RME-8 as a novel regulator.

Discrete GPCR-triggered endocytic modes enable β-arrestins to flexibly regulate cell signaling

This study identifies two distinct GPCR-triggered endocytic modes in β-arrestins, each with different signaling outcomes and receptor-specific activation.

Membrane phosphoinositides stabilize GPCR-arrestin complexes and offer temporal control of complex assembly and dynamics

This study identifies membrane phosphoinositides as regulators of GPCR-arrestin complex dynamics, showing they stabilize complexes and enable temporal control of receptor signaling and recycling.

Endosomal cAMP production broadly impacts the cellular phosphoproteome

The paper shows that endosomal cAMP production leads to distinct phosphoproteomic changes compared to plasma membrane cAMP, with a strong bias toward dephosphorylation by PP2A-B56{delta}.

A high-throughput CRISPR interference screen for dissecting functional regulators of GPCR/cAMP signaling

The paper develops a CRISPR interference screen to identify regulators of GPCR/cAMP signaling, identifying 45 strong and 50 weaker regulators, and validates seven novel mediators.

State-selective Modulation of Heterotrimeric Gαs Signaling with Macrocyclic Peptides

This study identifies two macrocyclic peptides that selectively modulate active and inactive states of Gs, offering a new approach for developing state-dependent GTPase inhibitors.

G protein-regulated endocytic trafficking of adenylyl cyclase type 9

This study shows AC9 traffics from the plasma membrane to endosomes via Gs, unlike AC1, and contributes to cAMP production from endosomes.

Agonist-selective recruitment of engineered protein probes and of GRK2 by opioid receptors in living cells

The paper develops a cell-based assay to study agonist-selective recruitment of engineered protein probes and GRK2 by opioid receptors in living cells, showing differential recruitment by distinct opioid ligands.