Specification of motoneurons from human embryonic stem cells.
AuthorsLi XJ, Du ZW, Zarnowska ED, Pankratz M, Hansen LO, Pearce RA, Zhang SC
JournalNat Biotechnol
PubMed ID15685164
'An understanding of how mammalian stem cells produce specific neuronal subtypes remains elusive. Here we show that human embryonic stem cells generated early neuroectodermal cells, which organized into rosettes and expressed Pax6 but not Sox1, and then late neuroectodermal cells, which formed neural tube-like structures and expressed both Pax6 and ... More
Local induction of acetylcholine receptor clustering in myotube cultures using microfluidic application of agrin.
AuthorsTourovskaia A, Kosar TF, Folch A
JournalBiophys J
PubMed ID16387765
'During neuromuscular synaptogenesis, the exchange of spatially localized signals between nerve and muscle initiates the coordinated focal accumulation of the acetylcholine (ACh) release machinery and the ACh receptors (AChRs). One of the key first steps is the release of the proteoglycan agrin focalized at the axon tip, which induces the ... More
Absence of acetylcholinesterase at the neuromuscular junctions of perlecan-null mice.
AuthorsArikawa-Hirasawa E, Rossi SG, Rotundo RL, Yamada Y
JournalNat Neurosci
PubMed ID11802174
'The collagen-tailed form of acetylcholinesterase (AChE) is concentrated at the vertebrate neuromuscular junction (NMJ), where it is responsible for rapidly terminating neurotransmission. This unique oligomeric form of AChE, consisting of three tetramers covalently attached to a collagen-like tail, is more highly expressed in innervated regions of skeletal muscle fibers, where ... More
Ex vivo imaging of motor axon dynamics in murine triangularis sterni explants.
AuthorsKerschensteiner M, Reuter MS, Lichtman JW, Misgeld T,
JournalNat Protoc
PubMed ID18833201
'We provide a protocol that describes an explant system that allows the dynamics of motor axons to be imaged. This method is based on nerve-muscle explants prepared from the triangularis sterni muscle of mice, a thin muscle that covers the inside of the thorax. These explants, which can be maintained ... More
alpha-Actinin interacts with rapsyn in agrin-stimulated AChR clustering.
AuthorsDobbins GC, Luo S, Yang Z, Xiong WC, Mei L,
JournalMol Brain
PubMed ID19055765
: AChR is concentrated at the postjunctional membrane at the neuromuscular junction. However, the underlying mechanism is unclear. We show that alpha-actinin, a protein known to cross-link F-actin, interacts with rapsyn, a scaffold protein essential for neuromuscular junction formation. alpha-Actinin, rapsyn, and surface AChR form a ternary complex. Moreover, the ... More
Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding.
AuthorsMcWhorter ML, Monani UR, Burghes AH, Beattie CE
JournalJ Cell Biol
PubMed ID12952942
Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by a loss of alpha motoneurons in the spinal cord. SMA is caused by low levels of the ubiquitously expressed survival motor neuron (Smn) protein. As it is unclear how low levels of Smn specifically affect motoneurons, we have modeled ... More
An essential ligand-binding domain in the membrane receptor for retinol-binding protein revealed by large-scale mutagenesis and a human polymorphism.
AuthorsKawaguchi R, Yu J, Wiita P, Honda J, Sun H,
JournalJ Biol Chem
PubMed ID18387951
Plasma retinol-binding protein (RBP), the principal carrier of vitamin A in the blood, delivers vitamin A from liver, the site of storage, to distant organs that need vitamin A, such as the eye, brain, placenta, and testis. STRA6 is a high-affinity membrane receptor for RBP and mediates vitamin A uptake ... More
Glial cells decipher synaptic competition at the mammalian neuromuscular junction.
AuthorsDarabid H, Arbour D, Robitaille R,
JournalJ Neurosci
PubMed ID23345206
It is now accepted that glial cells actively interact with neurons and modulate their activity in many regions of the nervous system. Importantly, modulation of synaptic activity by glial cells depends on the proper detection and decoding of synaptic activity. However, it remains unknown whether glial cells are capable of ... More
Myotubular myopathy and the neuromuscular junction: a novel therapeutic approach from mouse models.
AuthorsDowling JJ, Joubert R, Low SE, Durban AN, Messaddeq N, Li X, Dulin-Smith AN, Snyder AD, Marshall ML, Marshall JT, Beggs AH, Buj-Bello A, Pierson CR,
JournalDis Model Mech
PubMed ID22645112
Myotubular myopathy (MTM) is a severe congenital muscle disease characterized by profound weakness, early respiratory failure and premature lethality. MTM is defined by muscle biopsy findings that include centralized nuclei and disorganization of perinuclear organelles. No treatments currently exist for MTM. We hypothesized that aberrant neuromuscular junction (NMJ) transmission is ... More
Identification of a motif in the acetylcholine receptor beta subunit whose phosphorylation regulates rapsyn association and postsynaptic receptor localization.
At the neuromuscular junction, the acetylcholine receptor (AChR) is specifically clustered in the postsynaptic membrane via interactions with rapsyn and other scaffolding proteins. However, it remains unclear where these proteins bind on the AChR and how the interactions are regulated. Here, we define a phosphorylation-dependent binding site on the receptor ... More
Neurotransmitter receptor dynamics studied in vivo by reversible photo-unbinding of fluorescent ligands.
AuthorsAkaaboune M, Grady RM, Turney S, Sanes JR, Lichtman JW
JournalNeuron
PubMed ID12086635
We show that fluorescently tagged ligands with high affinity for their targets can be reversibly unbound by focused laser excitation. By sequential unbinding and relabeling with different colors of alpha-bungarotoxin, we selectively labeled adjacent pools of acetylcholine receptors (AChRs) at neuromuscular junctions of adult mice. Timelapse imaging in vivo revealed ... More
Nicotinic acetylcholine receptor is internalized via a Rac-dependent, dynamin-independent endocytic pathway.
AuthorsKumari S, Borroni V, Chaudhry A, Chanda B, Massol R, Mayor S, Barrantes FJ,
JournalJ Cell Biol
PubMed ID18591431
Endocytosis of the nicotinic acetylcholine receptor (AChR) is a proposed major mechanism of neuromodulation at neuromuscular junctions and in the pathology of synapses in the central nervous system. We show that binding of the competitive antagonist alpha-bungarotoxin (alphaBTX) or antibody-mediated cross-linking induces the internalization of cell surface AChR to late ... More
Nanoscale organization of nicotinic acetylcholine receptors revealed by stimulated emission depletion microscopy.
AuthorsKellner RR, Baier CJ, Willig KI, Hell SW, Barrantes FJ
JournalNeuroscience
PubMed ID17049171
Acetylcholine receptor (AChR) supramolecular aggregates that have hitherto only been accessible to examination by electron microscopy were imaged with stimulated emission depletion (STED) fluorescence microscopy, providing resolution beyond limits of diffraction of classical wide-field or confocal microscopes. We examined a Chinese hamster ovary cell liner CHO-K1/A5, that stably expresses adult ... More
Alpha1-syntrophin-deficient skeletal muscle exhibits hypertrophy and aberrant formation of neuromuscular junctions during regeneration.
AuthorsHosaka Y, Yokota T, Miyagoe-Suzuki Y, Yuasa K, Imamura M, Matsuda R, Ikemoto T, Kameya S, Takeda S
JournalJ Cell Biol
PubMed ID12221071
Alpha1-syntrophin is a member of the family of dystrophin-associated proteins; it has been shown to recruit neuronal nitric oxide synthase and the water channel aquaporin-4 to the sarcolemma by its PSD-95/SAP-90, Discs-large, ZO-1 homologous domain. To examine the role of alpha1-syntrophin in muscle regeneration, we injected cardiotoxin into the tibialis ... More
Effect of Bacillus anthracis lethal toxin on human peripheral blood mononuclear cells.
AuthorsPopov SG, Villasmil R, Bernardi J, Grene E, Cardwell J, Popova T, Wu A, Alibek D, Bailey C, Alibek K
JournalFEBS Lett
PubMed ID12220662
Lethal toxin (LeTx) plays a central role in anthrax pathogenesis, however a cytotoxicity of LeTx has been difficult to demonstrate in vitro. No cytolytic effect has been reported for human cells, in contrast to murine cell lines, indicating that cell lysis can not be considered as a marker of LeTx ... More
Disturbed Ca2+ kinetics in N-deacetylase/N-sulfotransferase-1 defective myotubes.
AuthorsJenniskens GJ, Ringvall M, Koopman WJ, Ledin J, Kjellén L, Willems PH, Forsberg E, Veerkamp JH, van Kuppevelt TH
JournalJ Cell Sci
PubMed ID12692154
The biosynthesis of heparan sulfate, present on the cell surface and in the basal lamina surrounding cells, is a multistep process in which each step is mediated by a specific enzyme. The initial modification of the precursor polysaccharide, N-deacetylation followed by N-sulfation of selected N-acetyl-D-glucosamine residues, is catalyzed by the ... More
Stem cell derived phenotypic human neuromuscular junction model for dose response evaluation of therapeutics.
Authors
JournalBiomaterials
PubMed ID29547745
Recovery of altered neuromuscular junction morphology and muscle function in mdx mice after injury.
Authors
JournalCell Mol Life Sci
PubMed ID24947322
Postnatal muscle modification by myogenic factors modulates neuropathology and survival in an ALS mouse model.
Authors
JournalNat Commun
PubMed ID24346342
FUS-mediated regulation of acetylcholine receptor transcription at neuromuscular junctions is compromised in amyotrophic lateral sclerosis.
Authors
JournalNat Neurosci
PubMed ID31591561
Dosage effect of multiple genes accounts for multisystem disorder of myotonic dystrophy type 1.
Authors
JournalCell Res
PubMed ID31853004
Control of CRK-RAC1 activity by the miR-1/206/133 miRNA family is essential for neuromuscular junction function.
Authors
JournalNat Commun
PubMed ID35676269
Boosting the peripheral immune response in the skeletal muscles improved motor function in ALS transgenic mice.
Authors
JournalMol Ther
PubMed ID35477657
Tethered agonist exposure in intact adhesion/class B2 GPCRs through intrinsic structural flexibility of the GAIN domain.
Authors
JournalMol Cell
PubMed ID33497605
The Atr-Chek1 pathway inhibits axon regeneration in response to Piezo-dependent mechanosensation.
Authors
JournalNat Commun
PubMed ID34158506
Piezo2 senses airway stretch and mediates lung inflation-induced apnoea.