Neuropilin-2/PlexinA3 Receptors Associate with GluA1 and Mediate Sema3F-Dependent Homeostatic Scaling in Cortical Neurons

Wang, Qiang; Chiu, Shu Ling; Koropouli, Eleftheria; Hong, Ingie; Mitchell, Sarah; Easwaran, Teresa; Hamilton, Natalie R.; Gustina, Ahleah S.; Zhu, Qianwen; Ginty, David D.; Huganir, Richard L.; Kolodkin, Alex L.

doi:10.1016/j.neuron.2017.10.029

Cited by 66 publications

(70 citation statements)

References 52 publications

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“…The neuronal pentraxin family of proteins interacts with the AMPAR N-terminal domain (118), with critical roles in maintaining synaptic AMPAR content in inhibitory interneurons (119) and retinal ganglion cells (120), but not CA1 pyramidal neurons (121). Neuropilin-2 binds to the extracellular N terminus of GluA1 through its two CUB domains (122), which is noteworthy because two different CUB domain-containing proteins, SOL-1 and SOL-2, have been identified as critical for functional surface expression of AMPARs in Caenorhabditis elegans (123,124). Moreover, two other CUB domain-containing proteins, NETO-1 and NETO-2, are auxiliary subunits of kainate receptors, which constitute another group of ionotropic glutamate receptor homologous AMPARs (125,126).…”

Section: Postsynaptic Anchoring Of Ampars By -Actininmentioning

confidence: 99%

“…Moreover, two other CUB domain-containing proteins, NETO-1 and NETO-2, are auxiliary subunits of kainate receptors, which constitute another group of ionotropic glutamate receptor homologous AMPARs (125,126). The neuropilin-2-GluA1 interaction is disrupted upon increased neuronal network activity in hippocampal cultures because of the activity-induced secretion of the neuropilin-2 agonist semaphorin 3F (122). This reduction in postsynaptic response depends on the Ras guanosine triphosphatase activating protein (GAP) activity of the cytosolic C terminus of PlexinA3, which dimerizes with neuropilin-2 in the AMPAR complex.…”

Section: Postsynaptic Anchoring Of Ampars By -Actininmentioning

confidence: 99%

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Mechanisms of postsynaptic localization of AMPA-type glutamate receptors and their regulation during long-term potentiation

et al. 2019

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l-Glutamate is the main excitatory neurotransmitter in the brain, with postsynaptic responses to its release predominantly mediated by AMPA-type glutamate receptors (AMPARs). A critical component of synaptic plasticity involves changes in the number of responding postsynaptic receptors, which are dynamically recruited to and anchored at postsynaptic sites. Emerging findings continue to shed new light on molecular mechanisms that mediate AMPAR postsynaptic trafficking and localization. Accordingly, unconventional secretory trafficking of AMPARs occurs in dendrites, from the endoplasmic reticulum (ER) through the ER-Golgi intermediary compartment directly to recycling endosomes, independent of the Golgi apparatus. Upon exocytosis, AMPARs diffuse in the plasma membrane to reach the postsynaptic site, where they are trapped to contribute to transmission. This trapping occurs through a combination of both intracellular interactions, such as TARP (transmembrane AMPAR regulatory protein) binding to -actinin-stabilized PSD-95, and extracellular interactions through the receptor amino-terminal domain. These anchoring mechanisms may facilitate precise receptor positioning with respect to glutamate release sites to enable efficient synaptic transmission.

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Section: Postsynaptic Anchoring Of Ampars By -Actininmentioning

confidence: 99%

Section: Postsynaptic Anchoring Of Ampars By -Actininmentioning

confidence: 99%

Mechanisms of postsynaptic localization of AMPA-type glutamate receptors and their regulation during long-term potentiation

et al. 2019

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“…Indeed, the related semaphorin Sema3E is present in the developing striatum and signals through PlexinD1 to establish thalamostriatal synapses on direct pathway SPNs (Ding et al, 2012). Furthermore, semaphorins have a recently described role in various forms of adult synaptic plasticity (Orr et al, 2017;Wang et al, 2017). Finally, semaphorin signaling could influence corticostriatal synapses by altering excitatory synapse formation in apical dendrites of Layer V neurons, which may have downstream effects on the corticostriatal synapse (Kozorovitskiy et al, 2012;Peixoto et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Neuropilin 2 signaling mediates corticostriatal transmission, spine maintenance, and goal-directed learning in mice

Assous

Martinez

Eisenberg

et al. 2019

Preprint

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The striatum represents the main input structure of the basal ganglia, receiving massive excitatory input from the cortex and the thalamus. The development and maintenance of cortical input to the striatum is crucial for all striatal function including many forms of sensorimotor integration, learning and action control. The molecular mechanisms regulating the development and maintenance of corticostriatal synaptic transmission are unclear. Here we show that the guidance cue, Semaphorin 3F and its receptor Neuropilin 2 (Nrp2), influence dendritic spine maintenance, corticostriatal short-term plasticity, and learning in adult male and female mice. We found that Nrp2 is enriched in adult layer V pyramidal neurons, corticostriatal terminals, and in developing and adult striatal spiny projection neurons (SPNs). Loss of Nrp2 increases SPN excitability and spine number, reduces short-term facilitation at corticostriatal synapses, and impairs goal-directed learning in an instrumental task. Acute deletion of Nrp2 selectively in adult layer V cortical neurons produces a similar increase in the number of dendritic spines and presynaptic modifications at the corticostriatal synapse in the Nrp2 -/mouse, but does not affect the intrinsic excitability of SPNs. Furthermore conditional loss of Nrp2 impairs sensorimotor learning on the accelerating rotarod without affecting goal-directed instrumental learning. Collectively, our results identify Nrp2 signaling as essential for the development and maintenance of the corticostriatal pathway and may shed novel insights on neurodevelopmental disorders linked to the corticostriatal pathway and semaphorin signaling. Significance StatementThe corticostriatal pathway controls sensorimotor, learning and action control behaviors and its dysregulation is linked to neurodevelopmental disorders, such as autism spectrum disorder (ASD). Here we demonstrate that neuropilin 2 (Nrp2), a receptor for the axon-guidance cue semaphorin 3F, has important and previously unappreciated functions in the development and adult maintenance of dendritic spines on striatal spiny projection neurons (SPNs), corticostriatal short-term plasticity, intrinsic physiological properties of SPNs and learning in mice. Our findings, coupled with Nrp2's association with ASD in human populations, suggest that Nrp2 may play an important role in ASD pathophysiology. Overall, our work demonstrates Nrp2 as a key regulator of corticostriatal development, maintenance and function, and may lead to better understanding of neurodevelopmental disease mechanisms.

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“…In addition, expression of PHP requires molecules that regulate vesicle release and the RRP size, such as RIM , Rab3-GAP (Muller et al, 2011), Dysbindin (Dickman and Davis, 2009), SNAP25 and Snapin (Dickman et al, 2012). Recent studies demonstrated that transsynaptic Semaphorin/Plexin interactions control synaptic scaling in cortical neurons in vertebrates (Wang et al, 2017) but also drive PHP at the fly NMJ (Orr et al, 2017). Neto-α may interact with one or several such presynaptic molecules and function as an effector of PHP.…”

Section: Discussionmentioning

confidence: 99%

Neto-α controls synapse organization and homeostasis at the Drosophila neuromuscular junction

Han

Vicidomini

Ramos

et al. 2019

Preprint

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Glutamate receptor auxiliary proteins control receptor distribution and function, ultimately controlling synapse assembly, maturation and plasticity. At the Drosophila neuromuscular junction (NMJ), a synapse with both pre-and post-synaptic kainate-type glutamate receptors (KARs), we show that the auxiliary protein Neto evolved functionally distinct isoforms to modulate synapse development and homeostasis. Using genetics, cell biology and electrophysiology we demonstrate that Neto-α functions on both sides of the NMJ. In muscle, Neto-α limits the size of the postsynaptic receptors field. In motor neurons, Neto-α controls neurotransmitter release in a KAR-dependent manner. Furthermore, Neto-α is both required and sufficient for the presynaptic increase in neurotransmitter release in response to reduced postsynaptic sensitivity. This KARindependent function of Neto-α is involved in activity-induced cytomatrix remodeling. We propose that Drosophila ensured NMJ functionality by acquiring two Neto isoforms with differential expression patterns and activities.

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Neuropilin-2/PlexinA3 Receptors Associate with GluA1 and Mediate Sema3F-Dependent Homeostatic Scaling in Cortical Neurons

Cited by 66 publications

References 52 publications

Mechanisms of postsynaptic localization of AMPA-type glutamate receptors and their regulation during long-term potentiation

Mechanisms of postsynaptic localization of AMPA-type glutamate receptors and their regulation during long-term potentiation

Neuropilin 2 signaling mediates corticostriatal transmission, spine maintenance, and goal-directed learning in mice

Neto-α controls synapse organization and homeostasis at the Drosophila neuromuscular junction

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