共 30 条
An SCF-like ubiquitin ligase complex that controls presynaptic differentiation
被引:177
作者:
Liao, EH
Hung, W
Abrams, B
Zhen, M
机构:
[1] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Med Genet & Microbiol, Toronto, ON M5G 1X5, Canada
[2] Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA
来源:
基金:
美国安德鲁·梅隆基金会;
美国国家科学基金会;
关键词:
D O I:
10.1038/nature02647
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:
During synapse formation, specialized subcellular structures develop at synaptic junctions in a tightly regulated fashion. Cross-signalling initiated by ephrins, Wnts and transforming growth factor-beta family members between presynaptic and postsynaptic termini are proposed to govern synapse formation(1-3). It is not well understood how multiple signals are integrated and regulated by developing synaptic termini to control synaptic differentiation. Here we report the identification of FSN-1, a novel F-box protein that is required in presynaptic neurons for the restriction and/or maturation of synapses in Caenorhabditis elegans. Many F-box proteins are target recognition subunits of SCF (Skp, Cullin, F-box) ubiquitin-ligase complexes(4-7). fsn-1 functions in the same pathway as rpm-1, a gene encoding a large protein with RING finger domains(8,9). FSN-1 physically associates with RPM-1 and the C. elegans homologues of SKP1 and Cullin to form a new type of SCF complex at presynaptic periactive zones. We provide evidence that T10H9.2, which encodes the C. elegans receptor tyrosine kinase ALK ( anaplastic lymphoma kinase(10)), may be a target or a downstream effector through which FSN-1 stabilizes synapse formation. This neuron-specific, SCF-like complex therefore provides a localized signal to attenuate presynaptic differentiation.
引用
收藏
页码:345 / 350
页数:6
相关论文