A transmembrane protein required for acetylcholine receptor clustering in Caenorhabditis elegans

被引:119
作者
Gally, C
Eimer, S
Richmond, JE
Bessereau, JL
机构
[1] Ecole Normale Super, INSERM, U497, F-75005 Paris, France
[2] Univ Illinois, Chicago, IL 60607 USA
关键词
D O I
10.1038/nature02893
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Clustering neurotransmitter receptors at the synapse is crucial for efficient neurotransmission. Here we identify a Caenorhabditis elegans locus, lev-10, required for postsynaptic aggregation of ionotropic acetylcholine receptors (AChRs). lev-10 mutants were identified on the basis of weak resistance to the anthelminthic drug levamisole, a nematode-specific cholinergic agonist that activates AChRs present at neuromuscular junctions (NMJs) resulting in muscle hypercontraction and death at high concentrations(1-3). In lev-10 mutants, the density of levamisole-sensitive AChRs at NMJs is markedly reduced, yet the number of functional AChRs present at the muscle cell surface remains unchanged. LEV-10 is a transmembrane protein localized to cholinergic NMJs and required in body-wall muscles for AChR clustering. We also show that the LEV-10 extracellular region, containing five predicted CUB domains and one LDLa domain, is sufficient to rescue AChR aggregation in lev-10 mutants. This suggests a mechanism for AChR clustering that relies on extracellular protein - protein interactions. Such a mechanism is likely to be evolutionarily conserved because CUB/LDL transmembrane proteins similar to LEV-10, but lacking any assigned function, are expressed in the mammalian nervous system and might be used to cluster ionotropic receptors in vertebrates.
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收藏
页码:578 / 582
页数:5
相关论文
共 28 条
  • [11] Gally C, 2003, J NEUROSCI, V23, P2591
  • [12] Lipoprotein receptors in the nervous system
    Herz, J
    Bock, HH
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 2002, 71 : 405 - 434
  • [13] LEWIS JA, 1980, GENETICS, V95, P905
  • [14] LEVAMISOLE-RESISTANT MUTANTS OF THE NEMATODE CAENORHABDITIS-ELEGANS APPEAR TO LACK PHARMACOLOGICAL ACETYLCHOLINE-RECEPTORS
    LEWIS, JA
    WU, CH
    LEVINE, JH
    BERG, H
    [J]. NEUROSCIENCE, 1980, 5 (06) : 967 - 989
  • [15] LEWIS JA, 1987, J NEUROSCI, V7, P3059
  • [16] eat-2 and eat-18 are required for nicotinic neurotransmission in the Caenorhabditis elegans pharynx
    McKay, JP
    Raizen, DM
    Gottschalk, A
    Schafer, WR
    Avery, L
    [J]. GENETICS, 2004, 166 (01) : 161 - 169
  • [17] A novel gene, Btcl1, encoding CUB and LDLa domains is expressed in restricted areas of mouse brain
    Michishita, M
    Ikeda, T
    Nakashiba, T
    Ogawa, M
    Tashiro, K
    Honjo, T
    Doi, K
    Itohara, S
    Endo, S
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 306 (03) : 680 - 686
  • [18] Miller T, 2000, J AGING PHYS ACTIV, V8, P289
  • [19] Synaptic clustering of AMPA receptors by the extracellular immediate-early gene product Narp
    O'Brien, RJ
    Xu, DS
    Petralia, RS
    Steward, O
    Huganir, RL
    Worley, P
    [J]. NEURON, 1999, 23 (02) : 309 - 323
  • [20] OKKEMA PG, 1993, GENETICS, V135, P385