Coordination of AMPA receptor trafficking by Rab GTPases

Abstract

Synaptic connections in the brain are continuously weakened or strengthened in response to changes in neuronal activity. This process, known as synaptic plasticity, is the cellular basis for learning and memory, and is thought to be altered in several neuronal disorders. An important aspect of synaptic plasticity is the tightly controlled trafficking and synaptic targeting of the AMPAtype glutamate receptors, which are the major mediators of fast excitatory transmission in the brain. This review addresses the role of Rab GTPases in AMPA receptor trafficking in neurons under basal conditions and during activity-induced synaptic plasticity, especially during long-term potentiation (LTP) and long-term depression (LTD). We highlight the importance of the tight spatio-temporal control of Rab activity and suggest that this is critical for proper neuronal functions. We also discuss how abnormal AMPA receptor trafficking and malfunctioning of Rabs can lead to neurologic disorders or memory problems.

Neurobeachin and the Kinesin KIF21B Are Critical for Endocytic Recycling of NMDA Receptors and Regulate Social Behavior

“…Studies have denoted the relevance for Rab-GTPase-mediated recycling to synaptic plasticity and cognitive function (Chiu et al, 2017;Hausser and Schlett, 2017). Besides their role in synaptic function and plasticity, GluN2B-NMDARs and NBEA are also essential for learning and memory (Nuytens et al, 2013;von Engelhardt et al, 2008;Yin et al, 2011).…”

P38α MAPK Signaling—A Robust Therapeutic Target for Rab5-Mediated Neurodegenerative Disease

“…In the context of neuronal function, a critical component of synaptic plasticity is the maintenance and/or recycling of AMPAR from the surface of synapses, [59] a process in which Rab proteins, including and particularly Rab5, through increasing endocytosis play a prominent role (Figure 1) [58]. In particular for the aspect of synaptic plasticity termed LTD, p38 MAPK activation facilitating AMPAR removal through increasing endocytosis via the Rab5-GDI complex has been demonstrated [56].…”

A Critical LRRK at the Synapse? The Neurobiological Function and Pathophysiological Dysfunction of LRRK2

“…LRRK2 is also implicated in SV storage and mobilization through its phosphorylation/binding of synapsin-I (Beccano-Kelly et al, 2014 ; Cirnaru et al, 2014 ; Carrion et al, 2017 ; Marte et al, 2019 ; Marku et al, 2020 ). (B) Cartoon of a generalized postsynaptic structure showing processes in which LRRK2 has been implicated, and which are also regulated by numerous Rab GTPases (reviewed in Hausser and Schlett, 2019 ). While altered neurotransmitter receptor (depicted in red) composition and structural plasticity have been observed in mutant LRRK2 models (Sweet et al, 2015 ; Matikainen-Ankney et al, 2018 ), much less is known about LRRK2’s physiological role in postsynaptic processes.…”