Cloning and characterization of a lambert‐eaton myasthenic syndrome antigen

Rosenfeld, Myrna R.; Wong, Edmund; Dalmau, Josep; Manley, Geoff; Jb, Posner; Sher, Emanuele; Furneaux, HM

doi:10.1002/ana.410330126

Cited by 66 publications

(29 citation statements)

References 39 publications

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“…Our findings also confirmed that the short N-terminal region was important for modification of inactivation kinetics, because ␤ 2a and ␤ 2c subunits were only different in this region. The N-terminal region of the rat ␤ 2c subunit was identical to those of a Lambert-Eaton myasthenic syndrome antigen and the human ␤ 2c subunit, except for some amino acids considered to be species differences (23,30). The similarity to the former protein raises the possibility that the rat ␤ 2c subunit was cloned from neuron, which innervated into heart.…”

Section: Discussionmentioning

confidence: 80%

Cloning of a Functional Splice Variant of L-type Calcium Channel β2 Subunit from Rat Heart

Yamada

Nagashima

Tsutsuura

et al. 2001

Journal of Biological Chemistry

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L-type Ca2؉ channels are heteromultimeric and finely tuned by auxiliary subunits in different tissues and regions. Among auxiliary subunits, ␤ subunit has been shown to play important roles in many functional aspects of Ca 2؉ channel. Rat heart was reported to specifically express ␤ 2a subunit. However, the slow inactivation rates of Ca 2؉ currents recorded from recombinant Ca 2؉ channels with the ␤ 2a subunit, and the reported inability to detect ␤ 2a subunit in rabbit heart by reverse transcription-PCR analysis raise the possibility of the existence of other ␤ subunits. We cloned a splice variant of ␤ 2 subunit from rat heart, using rapid amplification of cDNA 5 ends. The splice variant is highly similar to human ␤ 2c subunit that was cloned from human ventricle. Northern blot analysis detected the rat ␤ 2c subunit abundantly in rat heart and brain. The deduced amino acid sequence of the ␤ 2c subunit was different from that of the ␤ 2a subunit only in the N-terminal region. When the ␤ 2c subunit was expressed along with ␣ 1c and ␣ 2 ␦ subunits in baby hamster kidney cells, the inactivation rates were comparable with those from native cardiac myocytes, although those with the ␤ 2a subunit were slow. Taken together, these observations suggest that the ␤ 2c subunit is a functional ␤ 2 subunit expressed in heart and that the short N-terminal region plays a major role in modifying inactivation kinetics.

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Section: Discussionmentioning

confidence: 80%

Cloning of a Functional Splice Variant of L-type Calcium Channel β2 Subunit from Rat Heart

Yamada

Nagashima

Tsutsuura

et al. 2001

Journal of Biological Chemistry

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“…Some patients' antibodies also recognize cytoplasmic antigens (Viglione et at. 1992) which may be the fl-subunit of the Ca2+ channel (Rosenfeld et al 1993). …”

Section: Discussionmentioning

confidence: 99%

Inhibition of calcium currents and exocytosis by Lambert‐Eaton syndrome antibodies in human lung cancer cells.

Viglione

O’Shaughnessy

Kim

1995

The Journal of Physiology

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1. Human small-cell lung cancer (SCLC) cells are believed to express the antigens responsible for the production of pathological antibodies in the Lambert-Eaton syndrome (LES), a Ca2+ channel disorder in which quantal transmitter release from the motor nerve terminal is impaired. Whole-cell patch-clamp techniques were used to study the voltage-dependent Ca2P channels expressed by H146 SCLC cells and the effects of LES antibodies on these channels. The types of Ca2+ channels were determined using biophysical properties and pharmacological sensitivity to several antagonists. 5. To determine whether the LES antibodies are downregulating a specific type(s) of Ca2P channel, nicardipine (10 /sM), w-CgTX GVIA (1 uM) or w-AgTX IVA (100 nM) was applied to tumour cells that had been previously exposed to LES serum for 24 h. The most pronounced change was that wi-AgTX IVA was 38-84 % less effective at reducing ICa after the IgG treatment. The effectiveness of nicardipine was diminished by 18% after incubation with the LES antibodies, whereas the w)-CgTX GVIA was seen to be more effective. These results suggest that LES IgG downregulates P-type Ca2+ channels and, possibly, to a lesser extent L-type channels. 6. In view of recent evidence that P-type Ca2+ channels mediate cholinergic transmitter release at the mammalian neuromuscular junction (NMJ), the expression of P-type Ca2+ channels in the SCLC cells and the reactivity of LES IgG with these channels support the hypothesis that P-type Ca2P channels in these cancer cells may trigger the autoantibody production in this disorder. The antibodies so produced are implicated in the functional impairment of the Ca2+ channels characteristic of LES. § To whom correspondence should be addressed.

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“…Following the discovery of anti-GAD antibodies in SMS, a series of antibodies against intracellular presynaptic nerve (47).…”

Section: Nerve Terminal/vesicle-associated Antigensmentioning

confidence: 99%

Onconeural antigens and the paraneoplastic neurologic disorders: at the intersection of cancer, immunity, and the brain.

Darnell

1996

Proc. Natl. Acad. Sci. U.S.A.

257

132

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Paraneoplastic neurologic disorders (PNDs) are believed to be autoimmune neuronal degenerations that develop in some patients with systemic cancer. A series of genes encoding previously undiscovered neuronal proteins have been cloned using antiserum from PND patients. Identification of these onconeural antigens suggests a reclassification of the disorders into four groups: those in which neuromuscular junction proteins, nerve terminal/vesicleassociated proteins, neuronal RNA binding proteins, or neuronal signal-transduction proteins serve as target antigens. This review considers insights into basic neurobiology, tumor immunology, and autoimmune neuronal degeneration offered by the characterization of the onconeural antigens.

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Cloning and characterization of a lambert‐eaton myasthenic syndrome antigen

Cited by 66 publications

References 39 publications

Cloning of a Functional Splice Variant of L-type Calcium Channel β2 Subunit from Rat Heart

Cloning of a Functional Splice Variant of L-type Calcium Channel β2 Subunit from Rat Heart

Inhibition of calcium currents and exocytosis by Lambert‐Eaton syndrome antibodies in human lung cancer cells.

Onconeural antigens and the paraneoplastic neurologic disorders: at the intersection of cancer, immunity, and the brain.

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