Signal Regulatory Proteins (SIRPS) Are Secreted Presynaptic Organizing Molecules
Signal Regulatory Proteins (SIRPS) Are Secreted Presynaptic Organizing Molecules
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DOI：
10.1074/jbc.m805729200
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发表时间：
2008-12-05
影响因子：
4.8
通讯作者：
Sanes, Joshua R.
中科院分区：
文献类型：
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作者：
Umemori, Hisashi;Sanes, Joshua R.
化学突触的形成需要突触伙伴之间交换组织信号。利用培养神经元中突触囊泡聚集作为突触前分化的标志，我们从小鼠脑中纯化了候选的突触前组织者。一个主要的生物活性物质是信号调节蛋白α（SIRP-α）的胞外结构域，它是一种集中在突触的跨膜免疫球蛋白超家族成员。SIRP-α的胞外结构域以发育调节的方式被切割和脱落。SIRP-α的突触前组织活性部分由CD 47介导。SIRP-α同系物、SIRP-β和-γ也具有突触囊泡聚集活性。SIRP-α的作用与另一种突触前组织者FGF 22的作用不同：这两种蛋白质诱导不同大小的囊泡簇，促进神经突分支的能力不同，并通过不同的受体和信号通路起作用。SIRP家族蛋白可以与其他组织分子一起作用以形成突触。
Formation of chemical synapses requires exchange of organizing signals between the synaptic partners. Using synaptic vesicle aggregation in cultured neurons as a marker of presynaptic differentiation, we purified candidate presynaptic organizers from mouse brain. A major bioactive species was the extracellular domain of signal regulatory protein alpha(SIRP-alpha), a transmembrane immunoglobulin superfamily member concentrated at synapses. Theextracellular domain of SIRP-alpha is cleaved and shed in a developmentally regulated manner. The presynaptic organizing activity of SIRP-alpha is mediated in part by CD47. SIRP-alpha homologues, SIRP-beta and -gamma also have synaptic vesicle clustering activity. The effects of SIRP-alpha are distinct from those of another presynaptic organizer, FGF22: the two proteins induced vesicle clusters of different sizes, differed in their ability to promote neurite branching, and acted through different receptors and signaling pathways. SIRP family proteins may act together with other organizing molecules to pattern synapses.