Cell Reports (Nov 2024)
EGF-mediated Golgi dynamics and cell migration require CARP2
Abstract
Summary: In mammalian cells, the Golgi exists in ribbon architecture—individual stacks laterally linked to each other by tubular structures. Golgi architecture changes dynamically to cater to cellular needs. Loss of architecture is linked with pathological conditions like cancer and neurodegeneration. Not much is known about the regulators of Golgi dynamics. Here, we demonstrate that CARP2 (caspase-8- and caspase-10-associated RING-containing protein 2), an endosomal ubiquitin ligase and a known regulator of cell migration, modulates Golgi dynamics. Epidermal growth factor (EGF) treatment modestly increases CARP2 protein and disperses Golgi. An exogenous supply of CARP2 also leads to Golgi dispersal. Conversely, Golgi remains intact in CARP2 knockout (KO) cells upon EGF treatment. CARP2 variants defective in either endosomal association or ligase activity are unable to affect Golgi dispersal. Importantly, CARP2 targets Golgin45 for ubiquitination and degradation in EGF-stimulated cells. Collectively, our findings unravel the existence of crosstalk between endosomal ubiquitin signaling and Golgi dynamics.
