Regulation of G protein-coupled receptor trafficking and signaling by Rab GTPases

Esseltine, Jessica L.; Ferguson, Stephen S. G.

doi:10.4161/sgtp.24304

Cited by 13 publications

(9 citation statements)

References 37 publications

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“…Rab11 is a member of the Rab small GTPase protein family which plays critical roles in regulating transport, docking and fusion of vesicles with their target membranes (29,30). Rab11 associates with recycling endosomes, trans-Golgi membranes and secretory vesicles (31 -34).…”

Section: Introductionmentioning

confidence: 99%

The small GTPase Rab11 co-localizes with -synuclein in intracellular inclusions and modulates its aggregation, secretion and toxicity

Chutna¹,

Goncalves²,

Villar‐Piqué

et al. 2014

Human Molecular Genetics

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Alpha-synuclein (aSyn) misfolding and aggregation are pathological features common to several neurodegenerative diseases, including Parkinson's disease (PD). Mounting evidence suggests that aSyn can be secreted and transferred from cell to cell, participating in the propagation and spreading of pathological events. Rab11, a small GTPase, is an important regulator in both endocytic and secretory pathways. Here, we show that Rab11 is involved in regulating aSyn secretion. Rab11 knockdown or overexpression of either Rab11a wild-type (Rab11a WT) or Rab11a GDP-bound mutant (Rab11a S25N) increased secretion of aSyn. Furthermore, we demonstrate that Rab11 interacts with aSyn and is present in intracellular inclusions together with aSyn. Moreover, Rab11 reduces aSyn aggregation and toxicity. Our results suggest that Rab11 is involved in modulating the processes of aSyn secretion and aggregation, both of which are important mechanisms in the progression of aSyn pathology in PD and other synucleinopathies.

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Section: Introductionmentioning

confidence: 99%

The small GTPase Rab11 co-localizes with -synuclein in intracellular inclusions and modulates its aggregation, secretion and toxicity

Chutna¹,

Goncalves²,

Villar‐Piqué

et al. 2014

Human Molecular Genetics

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“…As briefly described above and thoroughly reviewed elsewhere (Dhami and Ferguson, 2006;Esseltine and Ferguson, 2013), there are reports indicating that mGlu5 receptors undergo agonist-dependent and -independent endocytosis that may or may not involve b-arrestin (Fourgeaud et al, 2003;Dhami and Ferguson, 2006;Ko et al, 2012). These data suggest that there are multiple complex mechanisms associated with trafficking and regulating mGlu5 receptor location.…”

Section: Discussionmentioning

confidence: 96%

Location-Dependent Signaling of the Group 1 Metabotropic Glutamate Receptor mGlu5

et al. 2014

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Although G protein-coupled receptors are primarily known for converting extracellular signals into intracellular responses, some receptors, such as the group 1 metabotropic glutamate receptor, mGlu5, are also localized on intracellular membranes where they can mediate both overlapping and unique signaling effects. Thus, besides "ligand bias," whereby a receptor's signaling modality can shift from G protein dependence to independence, canonical mGlu5 receptor signaling can also be influenced by "location bias" (i.e., the particular membrane and/or cell type from which it signals). Because mGlu5 receptors play important roles in both normal development and in disorders such as Fragile X syndrome, autism, epilepsy, addiction, anxiety, schizophrenia, pain, dyskinesias, and melanoma, a large number of drugs are being developed to allosterically target this receptor. Therefore, it is critical to understand how such drugs might be affecting mGlu5 receptor function on different membranes and in different brain regions. Further elucidation of the site(s) of action of these drugs may determine which signal pathways mediate therapeutic efficacy.

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“…Optineurin (OPTN) is co-localized with huntingtin (Htt) in the Golgi apparatus, forms a complex with Rab8, and participates in the regulation of post-Golgi protein transport (del Toro et al, 2009; Esseltine and Ferguson, 2013). OPTN has been identified as a binding molecule to the mGlu1a CTD in a yeast two-hybrid screen (Anborgh et al, 2005).…”

Section: Group I Mglu Receptorsmentioning

confidence: 99%

Metabotropic glutamate receptor trafficking

Suh

Chang

Roche

2018

Molecular and Cellular Neuroscience

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The metabotropic glutamate receptors (mGlu receptors) are G protein-coupled receptors that bind to the excitatory neurotransmitter glutamate and are important in the modulation of neuronal excitability, synaptic transmission, and plasticity in the central nervous system. Trafficking of mGlu receptors in and out of the synaptic plasma membrane is a fundamental mechanism modulating excitatory synaptic function through regulation of receptor abundance, desensitization, and signaling profiles. In this review, we cover the regulatory mechanisms determining surface expression and endocytosis of mGlu receptors, with particular focus on post-translational modifications and receptor-protein interactions. The literature we review broadens our insight into the precise events defining the expression of functional mGlu receptors at synapses, and will likely contribute to the successful development of novel therapeutic targets for a variety of developmental, neurological, and psychiatric disorders.

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Regulation of G protein-coupled receptor trafficking and signaling by Rab GTPases

Cited by 13 publications

References 37 publications

The small GTPase Rab11 co-localizes with -synuclein in intracellular inclusions and modulates its aggregation, secretion and toxicity

The small GTPase Rab11 co-localizes with -synuclein in intracellular inclusions and modulates its aggregation, secretion and toxicity

Location-Dependent Signaling of the Group 1 Metabotropic Glutamate Receptor mGlu5

Metabotropic glutamate receptor trafficking

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