Synaptic integrins in developing, adult, and mutant muscle: Selective association of alpha 1, alpha 7A, and alpha 7B integrins with the neuromuscular junction
Synaptic integrins in developing, adult, and mutant muscle: Selective association of alpha 1, alpha 7A, and alpha 7B integrins with the neuromuscular junction
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DOI：
10.1006/dbio.1996.0057
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发表时间：
1996-02-25
影响因子：
2.7
通讯作者：
Sanes, JR
中科院分区：
文献类型：
--
作者：
Martin, PT;Kaufman, SJ;Sanes, JR
骨骼肌神经肌肉接头处突触前和突触后结构的分化是由占据突触间隙的基底层组织的。由于β1整合素是基底层成分的一类主要受体，我们用已知能与β1形成二聚体的10种整合素α亚单位的抗体对肌肉进行染色，以确定这些分子中是否有任何一种集中在肌纤维的突触部位。在发育中的肌肉和成年肌肉中，整合素α1链选择性地与突触前细胞（施万细胞和/或神经末梢）相关联，而α7存在于肌纤维表面的突触和突触外部分。因此，α1和α7整合素存在于突触膜中。通过用对α7基因的三种可变剪接产物（A、B和C）特异的抗体染色，进一步分析了α7链的表达，这三种产物都在肌肉中表达。α7A和α7B异构体在成年肌肉中局限于突触部位，而α7C在突触和突触外均有存在。在发育中的肌肉中，α7A在出生后出现且特异性地位于突触处；α7B在围产期存在于整个肌纤维，在出生后第二周局限于突触；α7C在围产期和成年期均存在于突触外。因此，两种α7整合素是突触特异性的，并且这三种在单一细胞类型内都显示出不同的时空表达模式。最后，我们询问层粘连蛋白表达的扰动是否影响α7整合素的分布。在正常小鼠中，层粘连蛋白β2集中在突触基底层。在β2缺失突变小鼠中，α7A仍然存在于突触部位，但α7B缺失。这一结果提供了遗传学证据，表明基底层成分是整合素分布的一个决定因素。（C）1996学术出版社有限公司
Differentiation of both pre- and postsynaptic structures at the skeletal neuromuscular junction is organized by the basal lamina that occupies the synaptic cleft. As beta 1 integrins are a major class of receptors for basal lamina components, we stained muscles with antibodies to the 10 integrin alpha subunits known to form dimers with beta 1, to determine if any of these molecules were concentrated at synaptic sites on muscle fibers. In both developing and adult muscle, the integrin alpha 1 chain was selectively associated with presynaptic cells (Schwann cells and/or nerve terminals), while alpha 7 was present on both synaptic and extrasynaptic portions of the muscle fiber surface. Thus alpha 1 and alpha 7 integrins are present in synaptic membranes. Expression of the alpha 7 chain was analyzed further by staining with antibodies specific for three alternatively spliced products of the alpha 7 gene (A, B, and C), all of which were expressed in muscle. The alpha 7A and alpha 7B isoforms were confined to synaptic sites in adult muscle, while alpha 7C was present both synaptically and extrasynaptically. In developing muscle, alpha 7A appeared postnatally and specifically at the synapse; alpha 7B was present throughout the muscle fiber perinatally, becoming confined to the synapse in the second postnatal week; and alpha 7C was present extrasynaptically both perinatally and in adulthood. Thus, two of the alpha 7 integrins are synapse-specific, and all three show distinct spatiotemporal patterns of expression within a single cell type. Finally, we asked whether perturbation of laminin expression affected the distribution of the alpha 7 integrins. In normal mice, laminin beta 2 is concentrated in synaptic basal lamina. In beta 2-null mutant mice, alpha 7A was still present at synaptic sites, but alpha 7B was absent. This result provides genetic evidence that basal lamina composition is a determinant of integrin distribution. (C) 1996 Academic Press, Inc.