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.
引用
收藏
页码:578 / 582
页数:5
相关论文
共 28 条
  • [21] Acetylcholine receptors direct rapsyn clusters to the neuromuscular synapse in zebrafish
    Ono, F
    Mandel, G
    Brehm, P
    [J]. JOURNAL OF NEUROSCIENCE, 2004, 24 (24) : 5475 - 5481
  • [22] Induction of dendritic spines by an extracellular domain of AMPA receptor subunit GluR2
    Passafaro, M
    Nakagawa, T
    Sala, C
    Sheng, M
    [J]. NATURE, 2003, 424 (6949) : 677 - 681
  • [23] RAIZEN DM, 1995, GENETICS, V141, P1365
  • [24] Richmond JE, 1999, NAT NEUROSCI, V2, P791, DOI 10.1038/12160
  • [25] A novel gene encoding a putative transmembrane protein with two extracellular CUB domains and a low-density lipoprotein class A module:: isolation of alternatively spliced isoforms in retina and brain
    Stöhr, H
    Berger, C
    Fröhlich, S
    Weber, BHF
    [J]. GENE, 2002, 286 (02) : 223 - 231
  • [26] Dynamic interaction of stargazin-like TARPs with cycling AMPA receptors at synapses
    Tomita, S
    Fukata, M
    Nicoll, RA
    Bredt, DS
    [J]. SCIENCE, 2004, 303 (5663) : 1508 - 1511
  • [27] Yochem J, 1998, GENETICS, V149, P1323
  • [28] SOL-1 is a CUB-domain protein required for GLR-1 glutamate receptor function in C-elegans
    Zheng, Y
    Mellem, JE
    Brockie, PJ
    Madsen, DM
    Maricq, AV
    [J]. NATURE, 2004, 427 (6973) : 451 - 457