Biology subjects

Ory, S.

Publications and source records attributed to Ory, S..

2 recordsLinked to original sources

bioRxiv2019

The atypical Rho GTPase RhoU interacts with Intersectin-2 to regulate endosomal recycling pathways

Rho GTPases play a key role in various membrane trafficking processes. RhoU is an atypical small Rho GTPase related to Rac/Cdc42 which possesses unique N- and C-terminal domains that regulate its function and its subcellular localization. RhoU localized at the plasma membrane, on endosomes and in cell adhesion structures where it governs cell signalling, differentiation and migration. However, despite its endomembrane localization, RhoU function in vesicular trafficking has been unexplored. Here, we identified intersectins (ITSNs) as new binding partners for RhoU and showed that the second PxxP motif at the N-terminus of RhoU mediated interactions with SH3 domains of ITSNs. To evaluate the function of RhoU and ITSNs in vesicular trafficking, we used fluorescent transferrin as a cargo for uptake experiments. We showed that silencing of either RhoU or ITSN2, but not ITSN1 increased transferrin accumulation in early endosomes resulting from defect in fast vesicle recycling. Concomitantly, RhoU and ITSN2 colocalized to a subset of Rab4-positive vesicles suggesting that RhoU-ITSN2 interaction may occur on fast recycling endosomes to regulate the fate of vesicular cargos.

cell biology↗

bioRxiv2018

Heteromerization of endogenous mu and delta opioid receptors tunes mu opioid receptor signaling and trafficking

Increasing evidence indicates that native mu and delta opioid receptors can associate to form heteromers in discrete brain neuronal circuits. However, little is known about their signaling and trafficking. Using double fluorescent knock-in mice, we investigated the impact of neuronal co-expression on the internalization profile of mu and delta opioid receptors in primary hippocampal cultures and in vivo. We established ligand selective mu-delta co-internalization upon activation by exogenous ligands and provide evidence for mu-delta co-internalization by the endogenous opioid peptide met-enkephalin, but not {beta}-endorphin. Co-internalization was driven by the delta opioid receptor, required an active conformation of both receptors and led to sorting to the lysosomal compartment. This alteration in the mu opioid receptor intracellular fate was accompanied by sustained ERK1/2 phosphorylation. In addition, increased mu-delta neuronal co-localization in the rostral ventromedial medulla in a chronic neuropathic state suggests that mu-delta heteromers are involved in the regulation of nociceptive transmission

neuroscience↗