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C Iborra

Publications and source records attributed to C Iborra.

12 recordsLinked to original sources
PubMed2000

Synaptotagmin I and IV define distinct populations of neuronal transport vesicles.

Mammalian synaptotagmins constitute a multigene family of at least 11 membrane proteins. We have characterized synaptotagmin IV using antibodies directed against the C2A domain of the protein. Antibodies reacted specifically with a protein band that migrated as a 41-44 kDa doublet. Synaptotagmin IV expression was regulated throughout development. A strong decrease in the amount detected by Western blotting occurred between postnatal day 5 and adulthood, in agreement with studies on the expression of synaptotagmin IV transcripts. In subcellular fractionation, synaptotagmin IV was not detected in the synaptic vesicle-enriched fraction. Immunofluorescence microscopy was concordant with this finding. In 6-day-old rat cerebellum and cultured hippocampal neurons the subcellular distribution of synaptotagmin IV was clearly different from that of synaptotagmin I. Synaptotagmin IV displayed a punctate non-polarized distribution on neuronal extensions, whereas synaptotagmin I staining was essentially synaptic. Synaptotagmin IV staining was also observed in the soma in strong perinuclear fluorescent puncta superimposed on that of Golgi/TGN markers. Furthermore, synaptotagmin IV was seen in the proximal part of the growth cone domain and not in the microfilament-rich region which includes filopodia. Co-localizations with the adhesion molecules vinculin and zyxin at the proximal part of growth cones were observed. Synaptotagmin IV may thus be involved in the regulation of specific membrane-trafficking pathways during brain development.

Animals↗
PubMed2000

alpha-latrotoxin forms calcium-permeable membrane pores via interactions with latrophilin or neurexin.

In order to explore the mechanisms by which alpha-latrotoxin activates neurotransmitter release, we have characterized its effects by patch-clamp methods on cells heterologously expressing its receptors, latrophilin-1 or neurexin-Ialpha. Application of alpha-latrotoxin (1 nM) to cells expressing rat latrophilin or neurexin, but not mock-transfected cells, induced a cationic conductance. In cells expressing latrophilin, current development was slow in the absence of divalent cations, but was accelerated by Ca2+ or Mg2+. In cells expressing neurexin, alpha-latrotoxin did not elicit currents in the absence of Ca2+. The toxin-induced conductance was rectifying, persistent, permeable to monovalent and divalent cations, but blocked by La3+. Single-channel recording revealed a permanently open state, with the same unitary conductance irrespective of whether cells expressed latrophilin or neurexin. Therefore, while pore formation displayed differences consistent with the reported properties of alpha-latrotoxin binding to latrophilin and neurexin, the pores induced by alpha-latrotoxin had identical properties. These results suggest that after anchoring to either of its nerve terminal receptors, alpha-latrotoxin inserts into the membrane and constitutes a single type of transmembrane ion pore.

Animals↗
PubMed1999

Antibodies against the beta subunit of voltage-dependent calcium channels in Lambert-Eaton myasthenic syndrome.

Lambert-Eaton myasthenic syndrome is an autoimmune disease that impairs neuromuscular transmission. Several studies suggest that neurotransmitter release is reduced by an immune response directed against the calcium channel complex of nerve terminals. The immunoglobulin G fractions from Lambert-Eaton myasthenic syndrome patients immunoprecipitate solubilized neuronal N- and P/Q-type channels and in certain cases brain, skeletal and cardiac muscle L-type channels [El Far O. et al. (1995) J. Neurochem. 64, 1696-1702; Lennon V. A. and Lambert E. H. (1989) Mayo Clin. Proc. 64, 1498-1504; Sher E. et al. (1989) Lancet ii, 640-643; Suenaga A. et al. (1996) Muscle Nerve 19, 1166-1168]. These channel immunoprecipitation assays are considered as useful for the diagnosis of this syndrome. In this study, we demonstrate that two predominant neuronal voltage-dependent calcium channel beta subunits (beta3 and beta4, of mol. wt 58,000) are general targets of Lambert-Eaton myasthenic syndrome autoantibodies. Of 20 disease sera tested, 55% were able to immunoprecipitate 35S-labeled beta subunits. All five patients affected with small-cell lung carcinoma were positive for the beta-subunit immunoprecipitation assay. Interestingly, only a fraction of the beta-subunit-positive sera was also able to immunoprecipitate N- and P/Q-type channels, suggesting that several of the beta-subunit epitopes are masked in native channels. In accordance with this observation, we found that several beta-positive sera were able to prevent the interaction between calcium channel alpha1 and beta subunits in vitro. In cases where sera were able to immunoprecipitate beta subunits, N- and P/Q-type channels, the immunoprecipitation of both channel types was either partially or entirely mediated by beta-subunit antibodies. Our results suggest that assays based on the immunoprecipitation of beta subunits can be used as an additional test to assist in the diagnosis of Lambert-Eaton myasthenic syndrome.

Antibodies↗
PubMed1999

Redistribution of presynaptic proteins during alpha-latrotoxin-induced release of neurotransmitter and membrane retrieval at the frog neuromuscular junction.

Calcium-dependent exocytosis at the nerve terminal involves the synaptic core (SNARE) complex composed of the t-SNAREs syntaxin 1 and synaptosome-associated protein of 25 kDa (SNAP-25), and the v-SNARE vesicle-associated membrane protein (VAMP/synaptobrevin), a stable heterotrimer which can associate with the putative calcium sensor protein, synaptotagmin. The distribution of these proteins at the frog neuromuscular junction was examined by immunofluorescent staining and confocal microscopy following exocytosis induced by alpha-latrotoxin. Experiments were performed under conditions in which synaptic vesicle recycling was either maintained in balance with exocytosis, or completely blocked, or during recovery from block of endocytosis. When endocytosis was maintained, protein distribution was essentially identical to that of unstimulated nerve terminals, in which syntaxin 1 and SNAP-25 are localized to the presynaptic active zones coincident with the postsynaptic folds that contain a high density of acetylcholine receptors (AChRs). Block of endocytosis led to complete incorporation of vesicle proteins into the plasmalemma, and t-SNARE distribution was no longer restricted to active zones. Five minutes after the onset of recovery, both synaptic vesicle proteins and t-SNARE proteins were concentrated into small spots, in a similar pattern to that obtained following endocytosis of the vital styryl dye FM1-43. These findings are consistent with a model in which following sustained exocytosis, t-SNARE trafficking involves internalization and transit via a vesicular compartment before recycling to the presynaptic plasma membrane.

Animals↗
PubMed1997

Developmental regulation of synaptotagmin I, II, III, and IV mRNAs in the rat CNS.

Synaptotagmin I is an abundant synaptic vesicle protein that has an essential function in mediating Ca2+-triggered neurotransmitter release. We have analyzed the distribution of four neural synaptotagmin isoforms during postnatal development of the rat CNS by in situ hybridization. Synaptotagmin I, II, III, and IV genes have distinct patterns of spatiotemporal expression except in cerebellum granule cells, where the four transcripts were detected during the formation of parallel fiber/Purkinje cell synapses. Throughout development synaptotagmin I mRNAs were widely expressed in brain, whereas synaptotagmin II transcripts were predominant in spinal cord. At all stages synaptotagmin III mRNAs were expressed uniformly in most neurons examined, although at a low level. Synaptotagmin I, II, and III gene expressions mainly increased during development and persisted in adulthood, mirroring neuronal differentiation. Conversely, synaptotagmin IV transcripts were predominant during perinatal development in a heterogeneous population of neurons and subsequently were expressed uniformly at a low level. Intense labeling was observed in the hippocampal CA3 field and in the subiculum, but not in the CA1 field, of the newborn rat. In cerebral cortex, lamina-specific labeling was detected with a high expression in cell layer V. Only a small number of Purkinje cell clusters were labeled in the flocculus and paraflocculus of the cerebellum. Heterogeneous sets of neurons expressing synaptotagmin IV gene also were observed in spinal cord. We thus speculate that synaptotagmin IV may a play a role in the development of the mammalian nervous system.

Aging↗
PubMed1997

[Cutaneous tuberculosis. A study of 4 cases].

INTRODUCTION: The recent increase in the incidence of tuberculosis has led to the return of cutaneous forms of this disease. In addition, diagnosis can now be made rapidly using genoma amplification. CASE REPORT: Four cases of cutaneous tuberculosis are described in nonimmunosuppressed patients: two cases of lupus vulgaris, including one due to Mycobacterium africanum, and two others of gummas, including one associated with tuberculosis verrucosa. The diagnosis was suggested by epidemiological, clinical, histological and immunological findings and confirmed by culture of the bacilli in 3 cases and by genoma amplification in 1. DISCUSSION: These observations illustrate the difficulties encountered in determining the tuberculosis nature of skin lesions. The clinical presentation, differential diagnosis, the pathophysiology of this disease and the new interest in genoma amplification are discussed.

Adult↗
PubMed1996

[Cutaneous necrosis secondary to topical treatment of wart with 20 p. 100 glutaraldehyde solution].

INTRODUCTION: A commercial 20 p. 100 formulation of glutaraldehyde was recently introduced for the treatment of plantar warts. The rhinopharyngopulmonary toxicity of glutaraldehyde is well known. Allergic skin reactions may also occur. We report a case of necrosis of the pulp of the greater toe during normal use of this product. CASE REPORT: A 7-year-old child consulted for major, dry and painful necrosis of the pulp of the greater right toe. Clinical examination suggested a caustic lesion. The only agent which could be incriminated was a daily application of a 20 p. 100 glutaraldehyde solution every day for 8 weeks. Local application of liquid nitrogen immediately before beginning the glutaraldehyde treatment may have been a favoring factor. After 6 weeks of local antibiotherapy, the lesion had not completely healed. DISCUSSION: In France, warts are not usually treated with 20 p. 100 glutaraldehyde. Used extensively in Great Britain, there have apparently been no major accident at concentrations under 10 p. 100. The recent report by a Japanese group indicating the efficacy and safety of 20 p. 100 glutaraldehyde has led to renewed interest in this treatment: necrosis has never been reported. In our case the necrosis occurred after normal use of the product. The caustic effect appears to dominate (role of concentration, pH?). Incidents due to sensitization have also been reported. Repeated cases of this type have led to the withdrawal of the product from the market in December 1995.

Administration, Topical↗