Ras and Rab interactor 1 controls neuronal plasticity by coordinating dendritic filopodial motility and AMPA receptor turnover

Szíber, Zsófia; Liliom, Hanna; Morales, Carlos O. Oueslati; Ignácz, Attila; Rátkai, Anikó; Ellwanger, Kornelia; Link, Gisela; Szűcs, Attila; Haußer, Angelika; Schlett, Katalin

doi:10.1091/mbc.e16-07-0526

Cited by 22 publications

(24 citation statements)

References 53 publications

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“…Other Ras effector molecules potentially implicated in neurodegenerative processes such as AD and/or PD are RIN1 and Tiam1. Both of them control synaptic plasticity; RIN1 destabilizes synaptic connections by affecting the dendrite morphology and increasing the dendritic filopodial motility [ 35 ], whereas Tiam1 controls neurite outgrowth [ 36 ]. Tiam1 also controls the DA neuron differentiation [ 37 ].…”

Section: Small Gtpases Of the Ras Familymentioning

confidence: 99%

Small GTPases of the Ras and Rho Families Switch on/off Signaling Pathways in Neurodegenerative Diseases

Sastre

Montoro

Gálvez‐Martín

et al. 2020

IJMS

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Small guanosine triphosphatases (GTPases) of the Ras superfamily are key regulators of many key cellular events such as proliferation, differentiation, cell cycle regulation, migration, or apoptosis. To control these biological responses, GTPases activity is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and in some small GTPases also guanine nucleotide dissociation inhibitors (GDIs). Moreover, small GTPases transduce signals by their downstream effector molecules. Many studies demonstrate that small GTPases of the Ras family are involved in neurodegeneration processes. Here, in this review, we focus on the signaling pathways controlled by these small protein superfamilies that culminate in neurodegenerative pathologies, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Specifically, we concentrate on the two most studied families of the Ras superfamily: the Ras and Rho families. We summarize the latest findings of small GTPases of the Ras and Rho families in neurodegeneration in order to highlight these small proteins as potential therapeutic targets capable of slowing down different neurodegenerative diseases.

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Section: Small Gtpases Of the Ras Familymentioning

confidence: 99%

Small GTPases of the Ras and Rho Families Switch on/off Signaling Pathways in Neurodegenerative Diseases

Sastre

Montoro

Gálvez‐Martín

et al. 2020

IJMS

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“…e activation of Rab5 is regulated by GEFs, and the inactivation is regulated by GAPs [16]. GEFs contain the conserved Vps9 domains [17], which may catalyze the transformation of Rab5 between GDP-Rab5 and GTP-Rab5, such as Rabex-5 [18], RME-6 [19,20], RIN1 [21], and p85 [22][23][24]. GAPs regulate the activated state of Rab5, such as Rab-GAP5 [25], tuberin [26], and Armus/TBC-2 [27] (Table 1).…”

Section: The Basic Information Of Rab5mentioning

confidence: 99%

The Emerging Role of Rab5 in Membrane Receptor Trafficking and Signaling Pathways

Yuan

Song

2020

Biochemistry Research International

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Ras analog in brain (Rab) proteins are small guanosine triphosphatases (GTPases) that belong to the Ras-like GTPase superfamily, and they can regulate vesicle trafficking. Rab proteins alternate between an activated (GTP-bound) state and an inactivated (GDP-bound) state. Early endosome marker Rab5 GTPase, a key member of the Rab family, plays a crucial role in endocytosis and membrane transport. The activated-state Rab5 recruits its effectors and regulates the internalization and trafficking of membrane receptors by regulating vesicle fusion and receptor sorting in the early endosomes. In this review, we summarize the role of small Rab GTPases Rab5 in membrane receptor trafficking and the activation of signaling pathways, such as Ras/MAPK and PI3K/Akt, which ultimately affect cell growth, apoptosis, tumorigenesis, and tumor development. This review may provide some insights for our future research and novel therapeutic targets for diseases.

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“…35 During clathrin-mediated internalization, Rab5 regulates uncoating and directs internalized AMPARs toward early endosomes. 25,[35][36][37] In C. elegans neurons, there is an additional, clathrin-independent endocytosis of the GLR-1 AMPAR-type subunit. This Rab5-independent endocytosis is mediated by lipid rafts, and AMPARs endocytosed through this mechanism are recycled by Rab10.…”

Section: Rab Proteins Regulating Ampar Trafficking Under Basal Conditmentioning

confidence: 99%

“…62 The surface level of AMPARs and its downregulation during chemically evoked LTD in cultured hippocampal neurons was shown to be dependent on the intact Rab5 effector functions of Ras and Rab interactor protein 1 (RIN1), as well. 36 Internalized AMPARs are sorted along the recycling or retention pathways, according to neuronal activity. 48,61 Blockade of Rab7-dependent trafficking by the dominant-negative Rab7 N125I produced a significant reduction in the extent of LTD, 47 indicating that Rab7-driven trafficking of AMPARs to lysosomes is important during LTD.…”

Section: Rab Proteins Regulating Ampar Trafficking Under Ltdmentioning

confidence: 99%

“…[73][74][75][76] Although it is likely that alteration of Rab GTPase activity cause the deregulated AMPA receptor trafficking that contributes to these diseases, substantial evidence for this is still missing. In a recent paper, we have shown that the Rab5 GEF RIN1 enhances GluA1 endocytosis due to its Rab5 GEF activity and plays a critical role in AMPAR internalization upon LTD. 36 RIN1 is highly expressed within the dendrites of hippocampal neurons 77 and regulates EphA4 receptor internalization. 78 Importantly, RIN1 ¡/¡ mice have deficits in fear learning and extinction and were proposed as a potential model for posttraumatic stress disorder, characterized by enhanced retention of fear-related memories.…”

Section: Rab Proteins Regulating Ampar Trafficking Under Ltdmentioning

confidence: 99%

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Coordination of AMPA receptor trafficking by Rab GTPases

Haußer

Schlett

2017

Small GTPases

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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.

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Ras and Rab interactor 1 controls neuronal plasticity by coordinating dendritic filopodial motility and AMPA receptor turnover

Abstract: In hippocampal neurons, Ras and Rab interactor 1 (RIN1) hinders the formation of stable synaptic connections by increasing dendritic filopodial motility and regulates long-term depression by enhancing AMPA receptor endocytosis.

Cited by 22 publications

References 53 publications

Small GTPases of the Ras and Rho Families Switch on/off Signaling Pathways in Neurodegenerative Diseases

Small GTPases of the Ras and Rho Families Switch on/off Signaling Pathways in Neurodegenerative Diseases

The Emerging Role of Rab5 in Membrane Receptor Trafficking and Signaling Pathways

Coordination of AMPA receptor trafficking by Rab GTPases

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