Ral mediates activity-dependent growth of postsynaptic membranes via recruitment of the exocyst

Teodoro, Rita O.; Pekkurnaz, Gülçin; Nasser, Abdullah; Higashi-Kovtun, Misao E.; Balakireva, Maria; McLachlan, Ian G.; Camonis, Jacques; Schwarz, Thomas L.

doi:10.1038/emboj.2013.181

Cited by 5 publications

(11 citation statements)

References 52 publications

(68 reference statements)

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“…Ral regulation of the exocyst represents a control point for postsynaptic plasticity. In mammals, expression of activated RalA in hippocampal neurons increases dendritic spine density in an exocystdependent manner and increases Sec5 expression in spines (Teodoro et al, 2013).…”

Section: Postsynaptic Plasticitymentioning

confidence: 99%

Diverse Functions and Signal Transduction of the Exocyst Complex in Tumor Cells

Tanaka

Goto

Iino

2016

Journal Cellular Physiology

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The exocyst complex is a large conserved hetero-oligomeric complex that consists of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84 subunits. It has been implicated in the targeting of vesicles for regulated exocytosis in various cell types, and is also important for targeted exocytosis of post-Golgi transport vesicles to the plasma membrane. The exocyst complex is essential for membrane growth, secretion, and function during exocytosis and endocytosis. Moreover, the individual components of the complex are thought to act on specific biological processes, such as cytokinesis, ciliogenesis, apoptosis, autophagy, and epithelial-mesenchymal transition (EMT). As a result, recent studies suggest that the exocyst complex may be involved in several diseases such as kidney disease, neuropathogenesis, diabetes, and cancer. In this review, we focus on the diverse functions and cellular signaling pathways of the exocyst complex in various tumors. J. Cell. Physiol. 232: 939-957, 2017. © 2016 Wiley Periodicals, Inc.

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Section: Postsynaptic Plasticitymentioning

confidence: 99%

Diverse Functions and Signal Transduction of the Exocyst Complex in Tumor Cells

Tanaka

Goto

Iino

2016

Journal Cellular Physiology

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“…This phenotype is fully penetrant with every larvae analyzed in both ral mutants showing this defect in several larval segments. ral G0501 is a protein null mutant (Teodoro et al 2013) and ral EE1 harbors a point mutation that results in an amino acid substitution, Ser154Leu, within a conserved amino acid sequence predicted to be required for nucleotide binding (Eun et al 2006). We used anti-HRP to label the nerve outline and quantified the width of the ISN at muscle 4 (m4) region (see methods).…”

Section: Resultsmentioning

confidence: 99%

“…Importantly, because the rescue construct has an HA-tag we can assess where Ral is being expressed. Because Ral is known to localize to the plasma membrane irrespective of its nucleotide binding state (Teodoro et al 2013), we can extrapolate the morphology of wrapping glia. Our results clearly show that Ral expression in wrapping glia leads to a complete rescue of wrapping glia morphology (Figure 7B).…”

Section: Resultsmentioning

confidence: 99%

“…Given the nature of this process, genes involved in membrane addition are likely to be required. A pathway that has recurrently been reported to orchestrate the polarized targeting of vesicles and to regulate membrane growth events is the exocyst complex, via its interaction with the small GTPase Ral (Lee & Schwarz 2016; Teodoro et al 2013; Armenti et al 2014; Balasubramanian et al 2010; Patrício-Rodrigues & Teodoro 2018). The exocyst is an octameric protein complex conserved from yeast to human that is an effector to many GTPases, including Ral.…”

Section: Introductionmentioning

confidence: 99%

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Peripheral axonal ensheathment is regulated by Ral GTPase and the exocyst complex

Silva-Rodrigues

Patrício-Rodrigues

Sousa-Xavier

et al. 2019

Preprint

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16Axon ensheathment is fundamental for fast impulse conduction and the normal 17 physiological functioning of the nervous system. Defects in axonal insulation lead to 18 debilitating conditions, but despite its importance, the molecular players responsible are 19 poorly defined. Here, we identify Ral GTPase as a key player in axon ensheathment in 20 Drosophila larval peripheral nerves. We demonstrate through genetic analysis that Ral 21 action through the exocyst complex is sufficient and necessary in wrapping glial cells to 22 regulate their growth and development. We suggest that the Ral-exocyst pathway 23 controls the targeting of secretory vesicles for membrane growth or for the secretion of a 24 wrapping glia-specific factor that itself regulates growth. In summary, our findings 25 provide a new molecular understanding of the process by which axons are ensheathed 26 in vivo, a process critical for normal neuronal function. 27 28 29 93Sec8 has also been shown to contribute to myelin formation in culture (Bolis et al. 2009). 94Together, these data hint at a function for Ral and for the exocyst in the process of 95 axonal wrapping, but whether they are required for myelin formation or axonal 96 ensheathing, or whether they are in the same pathway, is not known. 4 98Here we show that Ral GTPase and the exocyst are critical regulators of nerve bundle 99 development in the Drosophila PNS. We demonstrate that ral mutants have severely 100 underdeveloped wrapping glia but have morphologically normal subperineurial and 101 perineurial glia, implying a specific role for Ral GTPase in wrapping glia and not in 102 general growth. We show that wrapping glia defects result from a failure to grow rather 103 than a failure to maintain membrane integrity. In addition, we demonstrate that these 104 mutants have thicker ISNs, often with defasciculated axons and signs of a disrupted 105 BNB. These defects in the mutants result in abnormal locomotion, possibly due to 106 altered axonal insulation. Genetic analyses show that Ral is both sufficient and 107 necessary in wrapping glia to regulate its growth and development. Furthermore, we 108 show that Ral GTPase functions via the exocyst complex in the regulation of these 109 developmental processes. Given the known roles of this pathway, we propose that the 110 Ral/exocyst pathway regulates axonal wrapping directly through the control of the 111 targeting of secretory vesicles for membrane addition or, alternatively, by controlling the 112 secretion of a wrapping glia-specific factor, that would itself regulate growth. In 113 summary, our findings establish Ral GTPase and the exocyst as novel players required 114 for wrapping glia development, and axonal ensheathment in vivo, a process critical for 115 normal impulse conduction. 116 117 118 5 Results 119 ral mutants have abnormal nerve bundles 120 Postembryonic PNS development requires substantial growth to accommodate the 121 increase in larval size. Specifically, PNS axons and their surrounding glial cells must 122 grow coordin...

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“…3). In terms of postsynaptic differentiation, which is also known to rely on transport packets of synaptic material (Washbourne et al 2002(Washbourne et al , 2004Sans et al 2003), the exocyst has a crucial role for the synaptic targeting and insertion of glutamate receptors (Gerges et al 2006) and for the growth of the postsynaptic membrane (Teodoro et al 2013).…”

Section: Presynaptic Differentiationmentioning

confidence: 99%

Puzzling out presynaptic differentiation

Pinto

Almeida

2016

Journal of Neurochemistry

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Proper brain function in the nervous system relies on the accurate establishment of synaptic contacts during development. Countless synapses populate the adult brain in an orderly fashion. In each synapse, a presynaptic terminal loaded with neurotransmitters-containing synaptic vesicles is perfectly aligned to an array of receptors in the postsynaptic membrane. Presynaptic differentiation, which encompasses the events underlying assembly of new presynaptic units, has seen notable advances in recent years. It is now consensual that as a growing axon encounters the receptive dendrites of its partner, presynaptic assembly will be triggered and specified by multiple postsynaptically-derived factors including soluble molecules and cell adhesion complexes. Presynaptic material that reaches these distant sites by axonal transport in the form of pre-assembled packets will be retained and clustered, ultimately giving rise to a presynaptic bouton. This review focuses on the cellular and molecular aspects of presynaptic differentiation in the central nervous system, with a particular emphasis on the identity of the instructive factors and the intracellular processes used by neuronal cells to assemble functional presynaptic terminals.

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Ral mediates activity-dependent growth of postsynaptic membranes via recruitment of the exocyst

Cited by 5 publications

References 52 publications

Diverse Functions and Signal Transduction of the Exocyst Complex in Tumor Cells

Diverse Functions and Signal Transduction of the Exocyst Complex in Tumor Cells

Peripheral axonal ensheathment is regulated by Ral GTPase and the exocyst complex

Puzzling out presynaptic differentiation

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