Auto-fusion and the shaping of neurons and tubes

Soulavie, Fabien; Sundaram, Meera V.

doi:10.1016/j.semcdb.2016.07.018

Cited by 14 publications

(13 citation statements)

References 99 publications

(159 reference statements)

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“…1d). This may be related to previously described defects in autofusion in eff-1 mutants [34][35][36] and suggests that miR-1-deficient animals have decreased expression or activity of EFF-1. Notably, trafficking and recycling of EFF-1 are altered upon V-ATPase loss-of-function in the C. elegans hypodermis 37,38 , providing a potential link.…”

supporting

confidence: 69%

A deeply conserved miR-1 dependent regulon supports muscle cell physiology

Gutiérrez-Pérez

Santillán

Lendl

et al. 2020

Preprint

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Muscles are not only essential for force generation but are also key regulators of systemic energy homeostasis1. Both these roles rely heavily on mitochondria and lysosome function as providers of energy and building blocks, but also as metabolic sensors2-4. Perturbations in these organelles or their crosstalk lead to a wide range of pathologies5. Here, we uncover a deeply conserved regulon of mitochondria and lysosome homeostasis under control of the muscle-specific microRNA miR-1. Animals lacking miR-1 display a diverse range of muscle cell defects that have been attributed to numerous different targets6. Guided by the striking conservation of miR-1 and some of its predicted targets, we identified a set of direct targets that can explain the pleiotropic function of miR-1. miR-1-mediated repression of multiple subunits of the vacuolar ATPase (V-ATPase) complex, a key player in the acidification of internal compartments and a hub for metabolic signaling7,8, and of DCT-1/BNIP3, a mitochondrial protein involved in mitophagy and apoptosis9,10, accounts for the function of this miRNA in C. elegans. Surprisingly, although multiple V-ATPase subunits are upregulated in the absence of miR-1, this causes a loss-of-function of V-ATPase due to altered levels or stoichiometry, which negatively impact complex assembly. Finally, we demonstrate the conservation of the functional relationship between miR-1 and the V-ATPase complex in Drosophila.

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supporting

confidence: 69%

A deeply conserved miR-1 dependent regulon supports muscle cell physiology

Gutiérrez-Pérez

Santillán

Lendl

et al. 2020

Preprint

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“…These single-pass transmembrane proteins mediate cell–cell fusion events to form syncytial tissues 20 – 22 , fuse gametes 26 , and allow viral infection of host cells 25 . EFF-1 and AFF-1 can also mediate cell auto-fusion to shape or repair neuronal dendrites and axons and to generate narrow seamless tubes with intracellular lumens 2 , 15 , 16 , 48 – 52 .…”

Section: Discussionmentioning

confidence: 99%

“…Finally, other studies in C . elegans revealed that a seamless tube can form by cell wrapping and self-contact to form a seamed tube with an autocellular junction, followed by auto-fusion to eliminate the junction and convert to a seamless toroid 2 , 15 – 17 . Auto-fusion may be a widely used mechanism, since it also generates some seamless tubes in the zebrafish vascular system 18 and in mammalian epithelial cells grown on micropillar arrays 19 ; however, relevant fusogens have not yet been identified in vertebrates.…”

Section: Introductionmentioning

confidence: 99%

The AFF-1 exoplasmic fusogen is required for endocytic scission and seamless tube elongation

2018

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Many membranes must merge during cellular trafficking, but fusion and fission events initiating at exoplasmic (non-cytosolic) membrane surfaces are not well understood. Here we show that the C. elegans cell–cell fusogen anchor-cell fusion failure 1 (AFF-1) is required for membrane trafficking events during development of a seamless unicellular tube. EGF-Ras-ERK signaling upregulates AFF-1 expression in the excretory duct tube to promote tube auto-fusion and subsequent lumen elongation. AFF-1 is required for scission of basal endocytic compartments and for apically directed exocytosis to extend the apical membrane. Lumen elongation also requires the transcytosis factor Rab11, but occurs independently of dynamin and clathrin. These results support a transcytosis model of seamless tube lumen growth and show that cell–cell fusogens also can play roles in intracellular membrane trafficking events.

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“…AFF-1, a paralog of EFF-1, is a second C. elegans fusogen displaying a more restricted tissue distribution pattern (Avinoam and Podbilewicz, 2011;Sapir et al, 2007); AFF-1 was not found to be involved in PVD remodeling during development (Oren-Suissa et al, 2017). AFF-1 and EFF-1 fusion proteins also auto-fuse epithelial and myoepithelial cells to form tubes and reshape glial cells (Procko et al, 2011;Rasmussen et al, 2008;Soulavie and Sundaram, 2016;Stone et al, 2009). Moreover, it has recently been demonstrated that in vertebrates auto-fusion takes place in the development of the vascular endothelium, where it leads to pruning of excess blood vessels (Lenard et al, 2015) in a process that remarkably resembles EFF-1-mediated PVD pruning (Oren-Suissa et al, 2010) and that may link EFF-1 to the actin cytoskeleton.…”

Section: Introductionmentioning

confidence: 99%

AFF-1 fusogen can rejuvenate the regenerative potential of adult dendritic trees via self-fusion

2017

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The aging brain undergoes structural changes that affect brain homeostasis, neuronal function and consequently cognition. The complex architecture of dendritic arbors poses a challenge to understanding age-dependent morphological alterations, behavioral plasticity and remodeling following brain injury. Here, we use the PVD polymodal neurons of C. elegans as a model to study how aging affects neuronal plasticity. Using confocal live imaging of C. elegans PVD neurons, we demonstrate age-related progressive morphological alterations of intricate dendritic arbors. We show that mutations in daf-2, which encodes an insulin-like growth factor receptor ortholog, fail to inhibit the progressive morphological aging of dendrites and do not prevent the minor decline in response to harsh touch during aging. We uncovered that PVD aging is characterized by a major decline in the regenerative potential of dendrites following experimental laser dendrotomy. Furthermore, the remodeling of transected dendritic trees by AFF-1-mediated self-fusion can be restored in old animals by daf-2 mutations, and can be differentially re-established by ectopic expression of the fusion protein AFF-1. Thus, ectopic expression of the fusogen AFF-1 in the PVD and mutations in daf-2 differentially rejuvenate some aspects of dendritic regeneration following injury.

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Auto-fusion and the shaping of neurons and tubes

Cited by 14 publications

References 99 publications

A deeply conserved miR-1 dependent regulon supports muscle cell physiology

A deeply conserved miR-1 dependent regulon supports muscle cell physiology

The AFF-1 exoplasmic fusogen is required for endocytic scission and seamless tube elongation

AFF-1 fusogen can rejuvenate the regenerative potential of adult dendritic trees via self-fusion

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