Spartin Regulates Synaptic Growth and Neuronal Survival by Inhibiting BMP-Mediated Microtubule Stabilization

Nahm, Minyeop; Lee, Min-Jung; Parkinson, William; Lee, Mihye; Kim, Hae Ran; Kim, Yun Joong; Kim, Sungdae; Cho, Yi Sul; Min, Byung‐Moo; Bae, Yong Chul; Broadie, Kendal; Lee, Seungbok

doi:10.1016/j.neuron.2012.12.015

Cited by 93 publications

(145 citation statements)

References 52 publications

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“…Impaired evoked transmitter release in atl 2 and Rtnl1 1 null mutants Altered levels of several HSP proteins, including Spartin and Spastin, alter transmitter release from Drosophila motor nerve terminals (Nahm et al, 2013;Ozdowski et al, 2011;Sherwood et al, 2004). We tested the possibility that atl 2 and Rtnl1 1 might similarly affect transmitter release.…”

Section: Bip-sfgfp-hdel Marks the Ermentioning

confidence: 99%

“…In addition to developmental functions, Drosophila BMP ligands released from muscle, peripheral glia or the motor neuron itself regulate transmitter release and synaptic growth in motor neurons (Fuentes-Medel et al, 2012;McCabe et al, 2003). Many HSP proteins, including Drosophila Spichthyin and Spartin, mammalian spastin and zebrafish atlastin, inhibit BMP signaling (Fassier et al, 2010;Nahm et al, 2013;Wang et al, 2007), possibly through altered BMP receptor trafficking. To determine whether Atl might similarly inhibit BMP signaling, we measured nuclear pMad within motor neuron nuclei of atl 2 third-instar larvae.…”

Section: Overexpression Of Atl In the Motor Neuron Impairs Neurotransmentioning

confidence: 99%

“…Drosophila mutant for any of several HSP orthologues similarly display behavioral deficits (Lee et al, 2008;Nahm et al, 2013;Sherwood et al, 2004). We used two assays to determine whether pan-neuronal atl inhibition generated locomotor deficits.…”

Section: Neuronal Loss Of Atl and Rtnl1 Causes Axon Terminal Overgrowthmentioning

confidence: 99%

“…For example, loss of spartin attenuates both ligand-stimulated EGF receptor uptake (Bakowska et al, 2007) as well as depolarization-stimulated FM1-43 uptake (Nahm et al, 2013), whereas loss of spastin increases endosome tubule number and alters transferrin receptor sorting (Allison et al, 2013). NIPA1 is also located in endosomes and promotes the endocytosis of receptors for bone morphogenetic protein (BMP) .…”

Section: Introductionmentioning

confidence: 99%

“…In Drosophila, loss of spastin, spartin and spichthyin confers a similar, but not identical, set of phenotypes including stabilized microtubules, increased synaptic bouton number and decreased evoked transmitter release at the larval neuromuscular junction (NMJ), age-dependent locomotor deficits and increased BMP signaling at the larval NMJ (Nahm et al, 2013;Ozdowski et al, 2011;Sherwood et al, 2004;Wang et al, 2007). These shared phenotypes might reflect disruption of a common pathway in endocytic receptor trafficking in these mutants.…”

Section: Introductionmentioning

confidence: 99%

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The effects of ER morphology on synaptic structure and function in Drosophila melanogaster

Summerville

Faust

Fan

et al. 2016

Journal of Cell Science

108

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Hereditary spastic paraplegia (HSP) is a set of genetic diseases caused by mutations in one of 72 genes that results in age-dependent corticospinal axon degeneration accompanied by spasticity and paralysis. Two genes implicated in HSPs encode proteins that regulate endoplasmic reticulum (ER) morphology. Atlastin 1 (ATL1, also known as SPG3A) encodes an ER membrane fusion GTPase and reticulon 2 (RTN2, also known as SPG12) helps shape ER tube formation. Here, we use a new fluorescent ER marker to show that the ER within wild-type Drosophila motor nerve terminals forms a network of tubules that is fragmented and made diffuse upon loss of the atlastin 1 ortholog atl. atl or Rtnl1 loss decreases evoked transmitter release and increases arborization. Similar to other HSP proteins, Atl inhibits bone morphogenetic protein (BMP) signaling, and loss of atl causes age-dependent locomotor deficits in adults. These results demonstrate a crucial role for ER in neuronal function, and identify mechanistic links between ER morphology, neuronal function, BMP signaling and adult behavior.

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Section: Bip-sfgfp-hdel Marks the Ermentioning

confidence: 99%

Section: Overexpression Of Atl In the Motor Neuron Impairs Neurotransmentioning

confidence: 99%

Section: Neuronal Loss Of Atl and Rtnl1 Causes Axon Terminal Overgrowthmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The effects of ER morphology on synaptic structure and function in Drosophila melanogaster

Summerville

Faust

Fan

et al. 2016

Journal of Cell Science

108

View full text Add to dashboard Cite

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Stability properties of neuronal microtubules

et al. 2016

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Neurons are terminally differentiated cells that use their microtubule arrays not for cell division but rather as architectural elements required for the elaboration of elongated axons and dendrites. In addition to acting as compression-bearing struts that provide for the shape of the neuron, microtubules also act as directional railways for organelle transport. The stability properties of neuronal microtubules are commonly discussed in the biomedical literature as crucial to the development and maintenance of the nervous system, and have recently gained attention as central to the etiology of neurodegenerative diseases. Drugs that affect microtubule stability are currently under investigation as potential therapies for disease and injury of the nervous system. There is often a lack of consistency, however, in how the issue of microtubule stability is discussed in the literature, and this can affect the design and interpretation of experiments as well as potential therapeutic regimens. Neuronal microtubules are considered to be more stable than microtubules in dividing cells. On average, this is true, but in addition to an abundant stable microtubule fraction in neurons, there is also an abundant labile microtubule fraction. Both are functionally important. Individual microtubules consist of domains that differ in their stability properties, and these domains can also differ markedly in their composition as well as how they interact with various microtubule-related proteins in the neuron. Myriad proteins and pathways have been discussed as potential contributors to microtubule stability in neurons.

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Tao Negatively Regulates BMP Signaling During Neuromuscular Junction Development in Drosophila

Politano

Salemme

Ashley

et al. 2019

Developmental Neurobiology

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The coordinated growth and development of synapses is critical for all aspects of neural circuit function and mutations that disrupt these processes can result in various neurological defects. Several anterograde and retrograde signaling pathways, including the canonical Bone Morphogenic Protein (BMP) pathway, regulate synaptic development in vertebrates and invertebrates. At the Drosophila larval neuromuscular junction (NMJ), the retrograde BMP pathway is a part of the machinery that controls NMJ expansion concurrent with larval growth. We sought to determine whether the conserved Hippo pathway, critical for proportional growth in other tissues, also functions in NMJ development. We found that neuronal loss of the serine‐threonine protein kinase Tao, a regulator of the Hippo signaling pathway, results in supernumerary boutons which contain a normal density of active zones. Tao is also required for proper synaptic function, as reduction of Tao results in NMJs with decreased evoked excitatory junctional potentials. Surprisingly, Tao function in NMJ growth is independent of the Hippo pathway. Instead, our experiments suggest that Tao negatively regulates BMP signaling as reduction of Tao leads to an increase in pMad levels in motor neuron nuclei and an increase in BMP target gene expression. Taken together, these results support a role for Tao as a novel inhibitor of BMP signaling in motor neurons during synaptic development and function.

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Spartin Regulates Synaptic Growth and Neuronal Survival by Inhibiting BMP-Mediated Microtubule Stabilization

Cited by 93 publications

References 52 publications

The effects of ER morphology on synaptic structure and function in Drosophila melanogaster

The effects of ER morphology on synaptic structure and function in Drosophila melanogaster

Stability properties of neuronal microtubules

Tao Negatively Regulates BMP Signaling During Neuromuscular Junction Development in Drosophila

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