Levels of Par-1 kinase determine the localization of Bruchpilot at the Drosophila neuromuscular junction synapses

Barber, Kara R.; Hruska, Martin; Bush, Keegan; Martinez, Jade A.; Fu, Hong; Levitan, Irwin B.; Dalva, Matthew B.; Wairkar, Yogesh P.

doi:10.1038/s41598-018-34250-9

Cited by 9 publications

(7 citation statements)

References 64 publications

(102 reference statements)

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“…Given the role of the cytoskeleton in AZ organization (Barber et al, 2018; Blunk et al, 2014; McNeill et al, 2020), STED was used to analyze the nanoscopic structure of Ib and Is AZs following disruption of several DEGs linked to cytoskeletal function. The Is-specific CG3085 protein encodes a Drosophila tektin of unknown function, although tektins are enriched in neurons and regulate microtubule stability in other species (Amos, 2008; Norrander et al, 1998).…”

Section: Resultsmentioning

confidence: 99%

Molecular Logic of Synaptic Diversity BetweenDrosophilaTonic and Phasic Motoneurons

Jetti

Crane

Akbergenova

et al. 2023

Preprint

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Although neuronal subtypes display unique synaptic organization and function, the underlying transcriptional differences that establish these features is poorly understood. To identify molecular pathways that contribute to synaptic diversity, single neuron PatchSeq RNA profiling was performed on Drosophila tonic and phasic glutamatergic motoneurons. Tonic motoneurons form weaker facilitating synapses onto single muscles, while phasic motoneurons form stronger depressing synapses onto multiple muscles. Super-resolution microscopy and in vivo imaging demonstrated synaptic active zones in phasic motoneurons are more compact and display enhanced Ca2+ influx compared to their tonic counterparts. Genetic analysis identified unique synaptic properties that mapped onto gene expression differences for several cellular pathways, including distinct signaling ligands, post-translational modifications and intracellular calcium buffers. These findings provide insights into how unique transcriptomes drive functional and morphological differences between neuronal subtypes.

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Section: Resultsmentioning

confidence: 99%

Molecular Logic of Synaptic Diversity BetweenDrosophilaTonic and Phasic Motoneurons

Jetti

Crane

Akbergenova

et al. 2023

Preprint

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“…Although there was no significant difference between average AZ number between controls and foxo mutants, we did observe more AZ's per bouton in the mutants. Previous studies have shown that accumulation of Brp in axons can limit active zone number at synaptic terminals (Barber et al, 2018 ). Foxo mutant larvae have been shown to have accumulations of Brp in the main axon (McLaughlin et al, 2016 ), but we were unable to capture this in the adult.…”

Section: Discussionmentioning

confidence: 98%

FOXO Regulates Neuromuscular Junction Homeostasis During Drosophila Aging

Birnbaum

Sodders

Bouska

et al. 2021

Front. Aging Neurosci.

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The transcription factor foxo is a known regulator of lifespan extension and tissue homeostasis. It has been linked to the maintenance of neuronal processes across many species and has been shown to promote youthful characteristics by regulating cytoskeletal flexibility and synaptic plasticity at the neuromuscular junction (NMJ). However, the role of foxo in aging neuromuscular junction function has yet to be determined. We profiled adult Drosophila foxo- null mutant abdominal ventral longitudinal muscles and found that young mutants exhibited morphological profiles similar to those of aged wild-type flies, such as larger bouton areas and shorter terminal branches. We also observed changes to the axonal cytoskeleton and an accumulation of late endosomes in foxo null mutants and motor neuron-specific foxo knockdown flies, similar to those of aged wild-types. Motor neuron-specific overexpression of foxo can delay age-dependent changes to NMJ morphology, suggesting foxo is responsible for maintaining NMJ integrity during aging. Through genetic screening, we identify several downstream factors mediated through foxo-regulated NMJ homeostasis, including genes involved in the MAPK pathway. Interestingly, the phosphorylation of p38 was increased in the motor neuron-specific foxo knockdown flies, suggesting foxo acts as a suppressor of p38/MAPK activation. Our work reveals that foxo is a key regulator for NMJ homeostasis, and it may maintain NMJ integrity by repressing MAPK signaling.

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“…Although there was no significant difference between average AZ number between controls and foxo mutants, we did observe more AZ’s per bouton in the mutants. Previous studies have shown that accumulation of Brp in axons can limit active zone number at synaptic terminals (Barber et al 2018). Foxo mutant larvae have been shown to have accumulations of Brp in the main axon (McLaughlin et al 2016), but we were unable to capture this in the adult.…”

Section: Discussionmentioning

confidence: 99%

FOXO regulates neuromuscular junction homeostasis duringDrosophilaaging

Birnbaum

Chang

Bai

2020

Preprint

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15The transcription factor FOXO is a known regulator of lifespan extension and tissue 16 homeostasis. It has been linked to the maintenance of neuronal processes across many species, and 17 has been shown to promote youthful characteristics by regulating cytoskeletal flexibility and 18 synaptic plasticity at the neuromuscular junction (NMJ). However, the role of FOXO in aging 19 neuromuscular junction function has yet to be determined. We profiled adult Drosophila null mutant abdominal ventral longitudinal muscles and found that young mutants exhibited 21 morphological profiles similar to those of aged wild-type flies, such as larger bouton areas and 22 shorter terminal branches. We also observed changes to the axonal cytoskeleton and an 23 accumulation of late endosomes in FOXO null mutants and motor neuron-specific FOXO 24 knockdown flies, similar to those of aged wild-types. Motor neuron-specific overexpression of 25 FOXO can delay age-dependent changes to NMJ morphology, suggesting FOXO is responsible 26 for maintaining NMJ integrity during aging. Through genetic screening, we identify several 27 downstream factors mediated through FOXO-regulated NMJ homeostasis, including genes 28 involved in the p38-MAPK pathway. Interestingly, the phosphorylation of p38 and ERK were 29 increased in the motor neuron-specific FOXO knockdown flies, suggesting FOXO acts as a 30 suppressor of MAPK activation. Our work reveals that FOXO is a key regulator for NMJ 31 homeostasis, and it maintains NMJ integrity by repressing MAPK signaling during aging.32 Introduction 33 Aging involves the progressive functional decline of cellular mechanisms and tissue 34 integrity (Rose 1994; Partridge and Barton 1996; Lopez-Otin et al 2013) In the adult brain, this 35 results in a gradual decline of synaptic contacts to skeletal muscle tissue, resulting in a loss of 36 strength and muscle mass (Hall and Sanes 1993). The neuromuscular junction (NMJ) serves as the 37 synaptic interface between the branched terminals of motor neurons and the skeletal muscle fibers 38 (Punga and Ruegg 2012). The NMJ is highly dynamic in response to cellular signals and stressors, 39 and a dysregulation of molecular processes in both the pre-and post-synaptic regions can lead to 40 the onset of neurodegenerative diseases (Gonzalez-Freire et al 2014; Monani and De Vivo 2014). 41 With aging there is impairment of regulatory systems such as autophagy and redox homeostasis at 42 the NMJ, which can lead to reactive oxygen species (ROS) accumulation followed by organelle 43 damage and cell death (Li et al 2018; Stefanatos and Sanz 2018). Synaptic plasticity, which allows 44 for the maintenance of functional activity to protect against degeneration, can decline during aging, 45 resulting in decreased neuronal responsiveness and synaptic deterioration (Bergado and 46 Anlmaguer 2002; Kempsell and Fieber 2015; Wagner et al 2015).47 76 1995; Liu et al 2013). These results indicate that FOXO is an important regulator of neuronal 77 function, and that it has influence on...

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Levels of Par-1 kinase determine the localization of Bruchpilot at the Drosophila neuromuscular junction synapses

Cited by 9 publications

References 64 publications

Molecular Logic of Synaptic Diversity BetweenDrosophilaTonic and Phasic Motoneurons

Molecular Logic of Synaptic Diversity BetweenDrosophilaTonic and Phasic Motoneurons

FOXO Regulates Neuromuscular Junction Homeostasis During Drosophila Aging

FOXO regulates neuromuscular junction homeostasis duringDrosophilaaging

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