Sleuthing molecular targets for neurological diseases at the neuromuscular junction

被引:112
作者
Engel, AG [1 ]
Ohno, K
Sine, SM
机构
[1] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA
[2] Mayo Clin, Neuromuscular Res Lab, Rochester, MN 55905 USA
[3] Mayo Clin, Dept Physiol & Biophys, Receptor Biol Lab, Rochester, MN 55905 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nrn1101
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The analysis of congenital myasthenic syndromes (CMSs) has disclosed a diverse array of molecular targets at the motor endplate and has delineated their contribution to synaptic function. Clinical, electrophysiological and morphological studies have paved the way for detecting CMS-related mutations in proteins such as choline acetyltransferase, acetylcholinesterase, the acetylcholine receptor and rapsyn, and studies of the mutant proteins have allowed us to correlate the effects of the mutations with predicted alterations in protein structure. Here, we review the symptomatology of CMSs, consider the factors that impair neuromuscular transmission, survey the mutations that have been uncovered in the different synaptic proteins, and consider the functional implications of the identified mutations.
引用
收藏
页码:339 / 352
页数:14
相关论文
共 129 条
[1]   A common mutation (ε1267delG) in congenital myasthenic patients of Gypsy ethnic origin [J].
Abicht, A ;
Stucka, R ;
Karcagi, V ;
Herczegfalvi, A ;
Horváth, R ;
Mortier, W ;
Schara, U ;
Ramaekers, V ;
Jost, W ;
Brunner, J ;
Janssen, G ;
Seidel, U ;
Schlotter, B ;
Müller-Felber, W ;
Pongratz, D ;
Rüdel, R ;
Lochmüller, H .
NEUROLOGY, 1999, 53 (07) :1564-1569
[2]   A newly identified chromosomal microdeletion and an N-box mutation of the AChRε gene cause a congenital myasthenic syndrome [J].
Abicht, A ;
Stucka, R ;
Schmidt, C ;
Briguet, A ;
Höpfner, S ;
Song, IH ;
Pongratz, D ;
Müller-Felber, W ;
Ruegg, MA ;
Lochmüller, H .
BRAIN, 2002, 125 :1005-1013
[3]   Absence of α-syntrophin leads to structurally aberrant neuromuscular synapses deficient in utrophin [J].
Adams, ME ;
Kramarcy, N ;
Krall, SP ;
Rossi, SG ;
Rotundo, RL ;
Sealock, R ;
Froehner, SC .
JOURNAL OF CELL BIOLOGY, 2000, 150 (06) :1385-1397
[4]   Heregulin‐stimulated acetylcholine receptor gene expression in muscle: requirement for MAP kinase and evidence for a parallel inhibitory pathway independent of electrical activity [J].
Nedret Altiok ;
Soner Altiok ;
Jean‐Pierre Changeux .
The EMBO Journal, 1997, 16 (4) :717-725
[5]   VOLTAGE CLAMP ANALYSIS OF ACETYLCHOLINE PRODUCED END-PLAT CURRENT FLUCTUATIONS AT FROG NEUROMUSCULAR-JUNCTION [J].
ANDERSON, CR ;
STEVENS, CF .
JOURNAL OF PHYSIOLOGY-LONDON, 1973, 235 (03) :655-691
[6]   Rapsyn is required for MuSK signaling and recruits synaptic components to a MuSK-containing scaffold [J].
Apel, ED ;
Glass, DJ ;
Moscoso, LM ;
Yancopoulos, GD ;
Sanes, JR .
NEURON, 1997, 18 (04) :623-635
[7]   Molecular cloning of a human, hemicholinium-3-sensitive choline transporter [J].
Apparsundaram, S ;
Ferguson, SM ;
George, AL ;
Blakely, RD .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 276 (03) :862-867
[8]   Absence of acetylcholinesterase at the neuromuscular junctions of perlecan-null mice [J].
Arikawa-Hirasawa, E ;
Rossi, SG ;
Rotundo, RL ;
Yamada, Y .
NATURE NEUROSCIENCE, 2002, 5 (02) :119-123
[9]   Interactions of the rapsyn RING-H2 domain with dystroglycan [J].
Bartoli, M ;
Ramarao, MK ;
Cohen, JB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (27) :24911-24917
[10]  
BARTOLI M, 2001, SOC NEUR ABSTR, V27