LRP4 serves as a coreceptor of agrin.


:Neuromuscular junction (NMJ) formation requires agrin, a factor released from motoneurons, and MuSK, a transmembrane tyrosine kinase that is activated by agrin. However, how signal is transduced from agrin to MuSK remains unclear. We report that LRP4, a low-density lipoprotein receptor (LDLR)-related protein, is expressed specifically in myotubes and binds to neuronal agrin. Its expression enables agrin binding and MuSK signaling in cells that otherwise do not respond to agrin. Suppression of LRP4 expression in muscle cells attenuates agrin binding, agrin-induced MuSK tyrosine phosphorylation, and AChR clustering. LRP4 also forms a complex with MuSK in a manner that is stimulated by agrin. Finally, we showed that LRP4 becomes tyrosine-phosphorylated in agrin-stimulated muscle cells. These observations indicate that LRP4 is a coreceptor of agrin that is necessary for MuSK signaling and AChR clustering and identify a potential target protein whose mutation and/or autoimmunization may cause muscular dystrophies.






Zhang B,Luo S,Wang Q,Suzuki T,Xiong WC,Mei L




Has Abstract


2008-10-23 00:00:00
















  • Pricking into Autonomic Reflex Pathways by Electrical Acupuncture.

    abstract::Using electrical acupuncture, Liu et al. show how electrical stimulation of primary somatosensory neurons at different body regions can tap into discreet autonomic circuits and, depending on the parameters, initiate either a pro- or anti-inflammatory response. ...


    pub_type: 评论,杂志文章


    authors: Kupari J,Ernfors P

    更新日期:2020-11-11 00:00:00

  • Memory Engram Cells Have Come of Age.

    abstract::The idea that memory is stored in the brain as physical alterations goes back at least as far as Plato, but further conceptualization of this idea had to wait until the 20(th) century when two guiding theories were presented: the "engram theory" of Richard Semon and Donald Hebb's "synaptic plasticity theory." While a ...


    pub_type: 杂志文章,评审


    authors: Tonegawa S,Liu X,Ramirez S,Redondo R

    更新日期:2015-09-02 00:00:00

  • Strange bedfellows: Reelin and Notch signaling interact to regulate cell migration in the developing neocortex.

    abstract::Neuronal cell migration in the developing neocortex relies on the Reelin signaling cascade to establish the characteristic "inside out" lamination pattern. In this issue of Neuron, Rakic and colleagues report that Notch signaling, long known to regulate neural stem cells, also plays a critical role in mediating the ef...


    pub_type: 评论,杂志文章,评审


    authors: Gaiano N

    更新日期:2008-10-23 00:00:00

  • p190RhoGAP Filters Competing Signals to Resolve Axon Guidance Conflicts.

    abstract::The rich functional diversity of the nervous system is founded in the specific connectivity of the underlying neural circuitry. Neurons are often preprogrammed to respond to multiple axon guidance signals because they use sequential guideposts along their pathways, but this necessitates a strict spatiotemporal regulat...


    pub_type: 杂志文章


    authors: Bonanomi D,Valenza F,Chivatakarn O,Sternfeld MJ,Driscoll SP,Aslanian A,Lettieri K,Gullo M,Badaloni A,Lewcock JW,Hunter T,Pfaff SL

    更新日期:2019-05-08 00:00:00

  • A Corticostriatal Balancing Act Supports Skill Learning.

    abstract::In this issue of Neuron, Kupferschmidt et al. (2017) reveal the shifting dynamics of functionally defined corticostriatal pathways during skill learning in mice using fiber photometry. They show different time courses in plasticity of associative and sensorimotor circuits across learning that involve changes at both t...


    pub_type: 杂志文章


    authors: Corbit VL,Ahmari SE,Gittis AH

    更新日期:2017-10-11 00:00:00

  • Microglia-derived nerve growth factor causes cell death in the developing retina.

    abstract::While nerve growth factor (NGF) is best known for its trophic functions, recent experiments indicate that it can also cause cell death during development by activating the neurotrophin receptor p75. We now identify microglial cells as the source of NGF as a killing agent in the developing eye. When the retina is separ...


    pub_type: 杂志文章


    authors: Frade JM,Barde YA

    更新日期:1998-01-01 00:00:00

  • What does it mean to be musical?

    abstract::Music can be seen as a model system for understanding gene × environment interactions and how these can influence neurocognitive development. The concept of musicality, however, is underspecified and not well understood. Here, I propose a framework for defining musicality to provide a foundation for studying the contr...


    pub_type: 杂志文章


    authors: Levitin DJ

    更新日期:2012-02-23 00:00:00

  • A lethal convergence of dopamine and calcium.

    abstract::The controversy about whether dopamine contributes to cell loss in Parkinson's disease takes a new turn as Mosharov et al. in this issue of Neuron demonstrate that Ca2+ influx through L-type channels elevates dopamine synthesis to potentially toxic levels in vulnerable ventral mesencephalon neurons. ...


    pub_type: 评论,杂志文章


    authors: Surmeier DJ

    更新日期:2009-04-30 00:00:00

  • Nna1 mediates Purkinje cell dendritic development via lysyl oxidase propeptide and NF-κB signaling.

    abstract::The molecular pathways controlling cerebellar Purkinje cell dendrite formation and maturation are poorly understood. The Purkinje cell degeneration (pcd) mutant mouse is characterized by mutations in Nna1, a gene discovered in an axonal regenerative context, but whose actual function in development and disease is unkn...


    pub_type: 杂志文章


    authors: Li J,Gu X,Ma Y,Calicchio ML,Kong D,Teng YD,Yu L,Crain AM,Vartanian TK,Pasqualini R,Arap W,Libermann TA,Snyder EY,Sidman RL

    更新日期:2010-10-06 00:00:00

  • Insulin-like growth factor I increases brain growth and central nervous system myelination in transgenic mice.

    abstract::Insulin-like growth factor I (IGF-I) is a potent regulator of oligodendrocyte development and myelination in vitro, but its effect on myelination in vivo has never been tested directly. Therefore, we examined brain growth and myelination in a transgenic mouse line that overexpresses IGF-I. By postnatal day 55, when br...


    pub_type: 杂志文章


    authors: Carson MJ,Behringer RR,Brinster RL,McMorris FA

    更新日期:1993-04-01 00:00:00

  • Orientation preference patterns in mammalian visual cortex: a wire length minimization approach.

    abstract::In the visual cortex of many mammals, orientation preference changes smoothly along the cortical surface, with the exception of singularities such as pinwheels and fractures. The reason for the existence of these singularities has remained elusive, suggesting that they are developmental artifacts. We show that singula...


    pub_type: 杂志文章


    authors: Koulakov AA,Chklovskii DB

    更新日期:2001-02-01 00:00:00

  • Natural scenes viewing alters the dynamics of functional connectivity in the human brain.

    abstract::Spontaneous fMRI fluctuations are organized in large-scale spatiotemporal structures, or resting-state networks (RSN). However, it is unknown how task performance affects RSN dynamics. We use MEG to measure slow (∼0.1 Hz) coherent fluctuations of band-limited power (BLP), a robust correlate of RSN, during rest and mov...


    pub_type: 杂志文章


    authors: Betti V,Della Penna S,de Pasquale F,Mantini D,Marzetti L,Romani GL,Corbetta M

    更新日期:2013-08-21 00:00:00

  • Synaptic homeostasis on the fast track.

    abstract::Synaptic homeostasis is a phenomenon that prevents the nervous system from descending into chaos. In this issue of Neuron, Frank et al. overturn the notion that synaptic homeostasis at Drosophila NMJs is a slow developmental process. They report that postsynaptic changes are offset within minutes by a homeostatic incr...


    pub_type: 评论,杂志文章,评审


    authors: Macleod GT,Zinsmaier KE

    更新日期:2006-11-22 00:00:00

  • Therapeutic deep brain stimulation in Parkinsonian rats directly influences motor cortex.

    abstract::Much recent discussion about the origin of Parkinsonian symptoms has centered around the idea that they arise with the increase of beta frequency waves in the EEG. This activity may be closely related to an oscillation between subthalamic nucleus (STN) and globus pallidus. Since STN is the target of deep brain stimula...


    pub_type: 杂志文章


    authors: Li Q,Ke Y,Chan DC,Qian ZM,Yung KK,Ko H,Arbuthnott GW,Yung WH

    更新日期:2012-12-06 00:00:00

  • Neuroscience and education: an ideal partnership for producing evidence-based solutions to Guide 21(st) Century Learning.

    abstract::Neuro-Education is a nascent discipline that seeks to blend the collective fields of neuroscience, psychology, cognitive science, and education to create a better understanding of how we learn and how this information can be used to create more effective teaching methods, curricula, and educational policy. Though stil...


    pub_type: 历史文章,杂志文章


    authors: Carew TJ,Magsamen SH

    更新日期:2010-09-09 00:00:00

  • TREM2 and Amyloid Beta: A Love-Hate Relationship.

    abstract::Mutations in TREM2 increase risk for late-onset AD. In this issue of Neuron, Zhao et al. (2018) show that TREM2 binds Aβ to enhance its clearance and Lee et al. (2018) demonstrate that human TREM2 expression in AD mice ameliorates Aβ-associated deficits. ...


    pub_type: 评论,杂志文章


    authors: Udeochu J,Sayed FA,Gan L

    更新日期:2018-03-07 00:00:00

  • Strong single-fiber sensory inputs to olfactory cortex: implications for olfactory coding.

    abstract::Olfactory information is first encoded in a combinatorial fashion by olfactory bulb glomeruli, which individually represent distinct chemical features of odors. This information is then transmitted to piriform (olfactory) cortex, via axons of olfactory bulb mitral and tufted (M/T) cells, where it is presumed to form t...


    pub_type: 杂志文章


    authors: Franks KM,Isaacson JS

    更新日期:2006-02-02 00:00:00

  • Psychopathology and the human connectome: toward a transdiagnostic model of risk for mental illness.

    abstract::The panoply of cognitive, affective, motivational, and social functions that underpin everyday human experience requires precisely choreographed patterns of interaction between networked brain regions. Perhaps not surprisingly, diverse forms of psychopathology are characterized by breakdowns in these interregional rel...


    pub_type: 杂志文章,评审


    authors: Buckholtz JW,Meyer-Lindenberg A

    更新日期:2012-06-21 00:00:00

  • Unmanageable motivation in addiction: a pathology in prefrontal-accumbens glutamate transmission.

    abstract::Prime diagnostic criteria for drug addiction include uncontrollable urges to obtain drugs and reduced behavioral responding for natural rewards. Cellular adaptations in the glutamate projection from the prefrontal cortex (PFC) to the nucleus accumbens have been discovered in rats withdrawn from cocaine that may underl...


    pub_type: 杂志文章,评审


    authors: Kalivas PW,Volkow N,Seamans J

    更新日期:2005-03-03 00:00:00

  • Networking: Translating Neuroscience to Public Policy.

    abstract::Neuroscientific findings are rarely translated into public policies that improve the health and well-being of people experiencing serious disorders. I advocate here for investment in policymaker-scientist networks dedicated to such translation for a range of diseases. ...


    pub_type: 杂志文章


    authors: Humphreys K

    更新日期:2019-09-25 00:00:00

  • Cerebellar Control of Reach Kinematics for Endpoint Precision.

    abstract::The cerebellum is well appreciated to impart speed, smoothness, and precision to skilled movements such as reaching. How these functions are executed by the final output stage of the cerebellum, the cerebellar nuclei, remains unknown. Here, we identify a causal relationship between cerebellar output and mouse reach ki...


    pub_type: 杂志文章


    authors: Becker MI,Person AL

    更新日期:2019-07-17 00:00:00

  • Public-private partnership: a new engine for translational research in neurosciences.

    abstract::We have made little recent progress developing effective new treatments for neuropsychiatric and neurodevelopmental disorders. Novel molecular mechanisms have been identified, but have not translated into the clinic. We suggest an alternative: combinations of treatments targeting different aspects of final common path...


    pub_type: 杂志文章


    authors: Murphy DG,Goldman M,Loth E,Spooren W

    更新日期:2014-11-05 00:00:00

  • Elucidating the Molecular Basis for Inhibitory Neurotransmission Regulation by Artemisinins.

    abstract::The frontline anti-malarial drug artemisinin and its derivatives have also been implicated in modulating multiple mammalian cellular pathways, including the recent identification of targeting γ-aminobutyric acid type A receptor (GABAAR) signaling in the pancreas. Their molecular mechanism of action, however, remains e...


    pub_type: 杂志文章


    authors: Kasaragod VB,Hausrat TJ,Schaefer N,Kuhn M,Christensen NR,Tessmer I,Maric HM,Madsen KL,Sotriffer C,Villmann C,Kneussel M,Schindelin H

    更新日期:2019-02-20 00:00:00

  • An Fgf8-dependent bistable cell migratory event establishes CNS asymmetry.

    abstract::Neuroanatomical and functional asymmetries are universal features of the vertebrate CNS, but how asymmetry is generated is unknown. Here we show that zebrafish fgf8 mutants do not elaborate forebrain asymmetries, demonstrated by the failure of the parapineal nucleus to migrate from its initial midline position to the ...


    pub_type: 杂志文章


    authors: Regan JC,Concha ML,Roussigne M,Russell C,Wilson SW

    更新日期:2009-01-15 00:00:00

  • It's not necessarily all about the delivery in Huntington's disease.

    abstract::Existing models of Huntington's disease posit that deficits in BDNF delivery to the striatum contribute to atrophy and motor impairment. In this issue of Neuron, Plotkin et al. (2014) show that BDNF delivery is normal but downstream signaling via TrkB and p75 is impaired, leading to corticostriatal synaptic dysfunctio...


    pub_type: 评论,杂志文章


    authors: Parsons MP,Raymond LA

    更新日期:2014-07-02 00:00:00

  • Genome-wide functional analysis of CREB/long-term memory-dependent transcription reveals distinct basal and memory gene expression programs.

    abstract::Induced CREB activity is a hallmark of long-term memory, but the full repertoire of CREB transcriptional targets required specifically for memory is not known in any system. To obtain a more complete picture of the mechanisms involved in memory, we combined memory training with genome-wide transcriptional analysis of ...


    pub_type: 杂志文章


    authors: Lakhina V,Arey RN,Kaletsky R,Kauffman A,Stein G,Keyes W,Xu D,Murphy CT

    更新日期:2015-01-21 00:00:00

  • Sensing without touching: psychophysical performance based on cortical microstimulation.

    abstract::Unequivocal proof that the activity of a localized cortical neuronal population provides sufficient basis for a specific cognitive function has rarely been obtained. We looked for such proof in monkeys trained to discriminate between two mechanical flutter stimuli applied sequentially to the fingertips. Microelectrode...


    pub_type: 杂志文章


    authors: Romo R,Hernández A,Zainos A,Brody CD,Lemus L

    更新日期:2000-04-01 00:00:00

  • Calcium-activated potassium channels expressed from cloned complementary DNAs.

    abstract::Calcium-activated potassium channels were expressed in Xenopus oocytes by injection of RNA transcribed in vitro from complementary DNAs derived from the slo locus of Drosophila melanogaster. Many cDNAs were found that encode closely related proteins of about 1200 aa. The predicted sequences of these proteins differ by...


    pub_type: 杂志文章


    authors: Adelman JP,Shen KZ,Kavanaugh MP,Warren RA,Wu YN,Lagrutta A,Bond CT,North RA

    更新日期:1992-08-01 00:00:00

  • The developmental origins of voice processing in the human brain.

    abstract::In human adults, voices are processed in specialized brain regions in superior temporal cortices. We examined the development of this cortical organization during infancy by using near-infrared spectroscopy. In experiment 1, 7-month-olds but not 4-month-olds showed increased responses in left and right superior tempor...


    pub_type: 杂志文章


    authors: Grossmann T,Oberecker R,Koch SP,Friederici AD

    更新日期:2010-03-25 00:00:00

  • The maintenance of LTP at hippocampal mossy fiber synapses is independent of sustained presynaptic calcium.

    abstract::We have examined the role of presynaptic residual calcium in maintaining long-term changes in synaptic efficacy observed at mossy fiber synapses between hippocampal dentate granule cells and CA3 pyramidal cells. Calcium concentrations in individual mossy fiber terminals in hippocampal slice were optically measured wit...


    pub_type: 杂志文章


    authors: Regehr WG,Tank DW

    更新日期:1991-09-01 00:00:00