The laminin alpha 2-chain short arm mediates cell adhesion through both the alpha 1 beta 1 and alpha 2 beta 1 integrins
The laminin alpha 2-chain short arm mediates cell adhesion through both the alpha 1 beta 1 and alpha 2 beta 1 integrins
复制标题
DOI：
10.1074/jbc.272.46.29330
复制
发表时间：
1997-11-14
影响因子：
4.8
通讯作者：
Yurchenco, PD
中科院分区：
文献类型：
--
作者：
Colognato, H;MacCarrick, M;Yurchenco, PD
层粘连蛋白-2是由α 2、β 1和γ 1亚基组成的异源三聚体，是在肌肉和外周神经中发现的主要层粘连蛋白同种型，并且对于这些组织中基底膜的发育和稳定性是必需的。结构域VI截短的层粘连蛋白α 2链的表达导致dy（2 J）营养不良小鼠中的肌肉变性和外周神经髓鞘形成障碍，我们表达了层粘连蛋白α 2链的氨基末端结构域VI至IVb，以及其层粘连蛋白-1 α 1链对应物，以鉴定该关键区域的候选细胞相互作用功能。使用整合素特异性抗体，在层粘连蛋白α 1-和α 2-链同种型的短臂中鉴定了α 1 β 1和α 2 β 1整联蛋白的识别位点，与具有β 1-链结构域VI的β-α嵌合短臂蛋白的比较进一步将这些活性定位于α-链结构域VI。此外，我们发现层粘连蛋白α 2-链短臂支持不依赖于其他层粘连蛋白-2亚基的神经突生长，肝素/硫酸乙酰肝素结合活性也定位于层粘连蛋白α 2亚基的该区域，这些数据提供了层粘连蛋白aa链结构域VI介导与细胞表面受体相互作用的第一个证据，并表明这些整合素和肝素结合位点，单独或共同，可能在肌肉和外周神经功能中发挥重要作用。
Laminin-2, a heterotrimer composed of alpha 2, beta 1, and gamma 1 subunits, is the primary laminin isoform found in muscle and peripheral nerve and is essential for the development and stability of basement membranes in these tissues, Expression of a domain VI-truncated laminin alpha 2-chain results in muscle degeneration and peripheral nerve dysmyelination in the dy(2J) dystrophic mouse, We have expressed amino-terminal domains VI through IVb of the laminin alpha 2-chain, as well as its laminin-1 alpha 1-chain counterpart, to identify candidate cell-interactive functions of this critical region, Using integrin-specific antibodies, recognition sites for the alpha 1 beta 1 and alpha 2 beta 1 integrins were identified in the short arms of both laminin alpha 1- and alpha 2-chain isoforms, Comparisons with a beta-alpha chimeric short arm protein possessing beta 1-chain domain VI further localized these activities to alpha-chain domain VI, In addition, we found that the laminin alpha 2-chain short arm supported neurite outgrowth independent of other laminin-2 subunits, A heparin/heparan sulfate binding activity was also localized to this region of the laminin alpha 2 subunit, These data provide the first evidence that domain VI of the laminin aa-chain mediates interactions with cell surface receptors and suggest that these integrin and heparin binding sites, alone or in concert, may play an important role in muscle and peripheral nerve function.