期刊
JOURNAL OF NEUROCHEMISTRY
卷 115, 期 3, 页码 654-666出版社
WILEY
DOI: 10.1111/j.1471-4159.2010.06965.x
关键词
synaptic laminins; voltage-gated calcium channels; neuromuscular Junction; active zones; bassonn; piccolo; nerve terminals
资金
- National Institutes of Health
- Muscular Dystrophy Assocation
P>At chemical synapses, synaptic cleft components interact with elements of the nerve terminal membrane to promote differentiation and regulate function. Laminins containing the beta 2 subunit are key cleft components, and they act in part by binding the pore-forming subunit of a pre-synaptic voltage-gated calcium channel (Ca-v alpha) (Nishimune et al. 2004). In this study, we identify Ca-v alpha-associated intracellular proteins that may couple channel-anchoring to assembly or stabilization of neurotransmitter release sites called active zones. Using Ca-v alpha-antibodies, we isolated a protein complex from Torpedo electric organ synapses, which resemble neuromuscular junctions but are easier to isolate in bulk. We identified 10 components of the complex: six cytoskeletal proteins (alpha 2/beta 2 spectrins, plectin 1, AHNAK/desmoyokin, dystrophin, and myosin 1), two active zone components (bassoon and piccolo), synaptic laminin, and a calcium channel beta subunit. Immunocytochemistry confirmed these proteins in electric organ synapses, and PCR analysis revealed their expression by developing mammalian motor neurons. Finally, we show that synaptic laminins also interact with pre-synaptic integrins containing the alpha 3 subunit. Together with our previous finding that a distinct synaptic laminin interacts with SV2 on nerve terminals (Son et al. 2000), our results identify three paths by which synaptic cleft laminins can send developmentally important signals to nerve terminals.
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