The effects of taipoxin and notexin on the function and fine structure of the murine neuromuscular junction

Cull-Candy, SG; Fohlman, Jan; Gustavsson, D.; Lüllmann‐Rauch, Renate; Thesleff, S.

doi:10.1016/0306-4522(76)90074-9

Cited by 141 publications

(65 citation statements)

References 9 publications

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“…Ultrastructurally the poisoned nerve terminals show the following lesions: reduction of the content of transmitter-storing vesicles, profuse f2-shaped indentations in the neurolemma, degenerative changes in the mitochondria and generally increased electron density with deposits of granular material. The data have been interpreted to indicate that the principal lesion caused by presynaptic snake venom neurotoxins is the inhibition of reformation of functional vesicles [3]. This hypothesis is supported by the observation that these toxins inhibit the high-affinity choline uptake of purified nerveterminal elements; namely, T-sacs (synaptosomes) from Torpedo marmorata [4].…”

Section: Introductionsupporting

confidence: 59%

Taipoxin, an extremely potent presynaptic snake venom neurotoxin Elucidation of the primary structure of the acidic carbohydrate‐containing taipoxin‐subunit, a prophospholipase homolog

Fohlman¹,

Lind²,

Eaker³

1977

FEBS Letters

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Section: Introductionsupporting

confidence: 59%

Taipoxin, an extremely potent presynaptic snake venom neurotoxin Elucidation of the primary structure of the acidic carbohydrate‐containing taipoxin‐subunit, a prophospholipase homolog

Fohlman¹,

Lind²,

Eaker³

1977

FEBS Letters

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“…At present, additional experiments are necessary to determine if variability in the molecular weight of NPR is due to use of alternative initiation sites, proteolytic cleavage of the putative amino-terminal transmembrane domain, or other post-translational modifications. DISCUSSION We have previously identified two major taipoxin-binding proteins, NP1 and TCBP49 (2,3), and suggested that they mediate the uptake and activation of taipoxin, a presynapticacting neurotoxin that blocks synaptic vesicle recycling (1,2). We have shown that the addition of NP1 to glial cultures renders them susceptible to taipoxin toxicity (2), supporting a direct interaction between taipoxin and NP1 and a role for NP1 in the uptake of taipoxin.…”

Section: Figmentioning

confidence: 91%

“…neusc.bcm.tmc.edu. 1 The abbreviations used are: NP1, neuronal pentraxin 1; NP2, neuronal pentraxin 2; TCBP49, taipoxin-associated calcium-binding protein 49; NPR, neuronal pentraxin receptor; GST, glutathione S-transferase; PCR, polymerase chain reaction; PAGE, polyacrylamide gel electrophoresis; Tricine, N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycine; kb, kilobase(s). equilibration buffer.…”

Section: Methodsmentioning

confidence: 99%

“…We identified two taipoxin binding proteins for a presynaptic-acting snake venom neurotoxin, taipoxin, that blocks recycling of synaptic vesicles (1,2). Affinity chromatography of solubilized rat brain membranes on columns of immobilized taipoxin enriches two major proteins: (i) neuronal pentraxin 1 (NP1), 1 a neuronally secreted protein with homology to serum pentraxins (2), and (ii) taipoxin-associated calcium-binding protein 49 (TCBP49), a reticular calcium-binding protein (3).…”

mentioning

confidence: 99%

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Neuronal Pentraxin Receptor, a Novel Putative Integral Membrane Pentraxin That Interacts with Neuronal Pentraxin 1 and 2 and Taipoxin-associated Calcium-binding Protein 49

Dodds

Omeis

Cushman

et al. 1997

Journal of Biological Chemistry

141

165

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We have identified the first putative integral membrane pentraxin and named it neuronal pentraxin receptor (NPR). NPR is enriched by affinity chromatography on columns of a snake venom toxin, taipoxin, and columns of the taipoxin-binding proteins neuronal pentraxin 1 (NP1), neuronal pentraxin 2 (NP2), and taipoxinassociated calcium-binding protein 49 (TCBP49). The predominant form of NPR contains an putative NH 2 -terminal transmembrane domain and all forms of NPR are glycosylated. NPR has 49 and 48% amino acid identity to NP1 and NP2, respectively, and NPR message is expressed in neuronal regions that express NP1 and NP2. We suggest that NPR, NP1, NP2, and TCBP49 are involved in a pathway responsible for the transport of taipoxin into synapses and that this may represent a novel neuronal uptake pathway involved in the clearance of synaptic debris.We identified two taipoxin binding proteins for a presynaptic-acting snake venom neurotoxin, taipoxin, that blocks recycling of synaptic vesicles (1, 2). Affinity chromatography of solubilized rat brain membranes on columns of immobilized taipoxin enriches two major proteins: (i) neuronal pentraxin 1 (NP1), 1 a neuronally secreted protein with homology to serum pentraxins (2), and (ii) taipoxin-associated calcium-binding protein 49 (TCBP49), a reticular calcium-binding protein (3). NP1 has homology to previously identified pentraxins, such as serum amyloid P protein and C-reactive protein, which are elevated in the serum during acute phase response. Although the exact functions of these previously identified pentraxins are not known, they have been shown to bind, in a calcium-dependent manner, a wide variety of ligands and have been proposed to mediate the uptake of bacteria, toxins, and extracellular debris (4, 5). Homology to serum pentraxins, as well as the presence of a cleaved signal peptide and N-linked glycosylation sites, suggests that NP1 is secreted. The abundance of NP1 mRNA and rarity of NP1 protein suggest that NP1 protein has a rapid turnover. We have proposed that NP1 has a role in uptake at the synapse and that NP1 mediates the uptake of taipoxin into neurons. By low stringency screening, we identified an additional neuronal pentraxin (NP2) in human that has 54% amino acid identity with NP1 and is expressed in brain and multiple other tissues (6). Potential homologs of NP2 have been identified in guinea pig as a sperm acrosomal protein, apexin/p50 (7,8), and in rat as a neural activity-regulated pentraxin, narp (9). The second taipoxin-binding protein, TCBP49, binds calcium via six EF-hand calcium binding motifs and is localized to the lumen of reticular membranes in neurons and glia (3). It contains the carboxyl-terminal sequence HDEL which has been shown to occasionally mediate endoplasmic reticulum retention in mammalian cells (10 -12). We have suggested that NP1 binds to synaptic material and is taken up into a compartment containing TCBP49 (2, 3). We have also suggested that NP1 allows the internalization of taipoxin or a taipoxin⅐NP1 complex and t...

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“…Electron microscopy performed at the third stage shows swollen and enlarged axon terminals with depletion of synaptic vesicles (SVs) [1,[9][10][11][12][13]. We recently showed that SPANs block the neurotransmission by promoting fusion of SVs with the presynaptic membrane and by inhibiting their retrieval, at the same time [14,15].…”

Section: Introductionmentioning

confidence: 99%

Reversible skeletal neuromuscular paralysis induced by different lysophospholipids

et al. 2006

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Lysophosphatidylcholine rapidly paralyses the neuromuscular junction (NMJ), similarly to snake phospholipase A2 neurotoxins, implicating a lipid hemifusion-pore transition in neuroexocytosis. The mode and kinetics of NMJ paralysis of different lysophospholipids (lysoPLs) in high or low [Mg 2+ ] was investigated. The following order of potency was found: lysophosphatidylcholine > lysophosphatidylethanolamine > lysophosphatidic acid > lysophosphatidylserine > lysophosphatidylglycerol. The latter two lysoPLs closely mimic the profile of paralysis caused by the toxins in high [Mg 2+ ]. This paralysis is fully reversed by albumin washing. These findings provide novel insights on the mode of action of snake neurotoxins and qualify lysoPLs as novel agents to study neuroexocytosis.

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The effects of taipoxin and notexin on the function and fine structure of the murine neuromuscular junction

Cited by 141 publications

References 9 publications

Taipoxin, an extremely potent presynaptic snake venom neurotoxin Elucidation of the primary structure of the acidic carbohydrate‐containing taipoxin‐subunit, a prophospholipase homolog

Taipoxin, an extremely potent presynaptic snake venom neurotoxin Elucidation of the primary structure of the acidic carbohydrate‐containing taipoxin‐subunit, a prophospholipase homolog

Neuronal Pentraxin Receptor, a Novel Putative Integral Membrane Pentraxin That Interacts with Neuronal Pentraxin 1 and 2 and Taipoxin-associated Calcium-binding Protein 49

Reversible skeletal neuromuscular paralysis induced by different lysophospholipids

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