Pillai Anilkumar M, Garcia-Fresco German P, Sousa Aurea D, Dupree Jeffrey L, Philpot Benjamin D, Bhat Manzoor A
Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
J Neurosci Res. 2007 Aug 15;85(11):2318-31. doi: 10.1002/jnr.21374.
Myelinated axons are endowed with a specialized domain structure that is essential for saltatory action potential conduction. The paranodal domain contains the axoglial junctions and displays a unique ultrastructure that resembles the invertebrate septate junctions (SJs). Biochemical characterizations of the paranodal axoglial SJs have identified several molecular components that include Caspr and contactin (Cont) on the axonal side and neurofascin 155 kDa (NF155) isoform on the glial side. All these proteins are essential for the formation of the axoglial SJs. Based on the interactions between Caspr and Cont and their colocalization in the CA1 synaptic areas, it was proposed that the synaptic function of Cont requires Caspr. Here we have extended the phenotypic analysis of CASPR mutants to address further the role of Caspr at the axoglial SJs and also in axonal orientation and synaptic plasticity. We report that, in CASPR mutants, the smooth endoplasmic reticulum (SER) forms elongated membranous complexes that accumulate at the nodal/paranodal region and stretch into the juxtaparanodal region, a defect that is consistent with the paranodal disorganization. We show that the cerebellar microorganization is unaffected in CASPR mutants. We also demonstrate that Caspr function is not essential for normal CA1 synaptic transmission and plasticity. Taken together with previous findings, our results highlight that the Caspr/Cont complex is essential for the formation of axoglial SJs, whereas Cont may regulate axonal orientation and synaptic plasticity independent of its association with Caspr.
有髓轴突具有一种特殊的结构域结构，这对于跳跃式动作电位传导至关重要。结旁结构域包含轴突-胶质连接，并呈现出一种独特的超微结构，类似于无脊椎动物的分隔连接（SJs）。结旁轴突-胶质SJs的生化特征已鉴定出几种分子成分，包括轴突侧的Caspr和接触蛋白（Cont）以及胶质侧的155 kDa神经束蛋白（NF155）异构体。所有这些蛋白质对于轴突-胶质SJs的形成都是必不可少的。基于Caspr和Cont之间的相互作用及其在CA1突触区域的共定位，有人提出Cont的突触功能需要Caspr。在这里，我们扩展了对CASPR突变体的表型分析，以进一步探讨Caspr在轴突-胶质SJs以及轴突定向和突触可塑性中的作用。我们报告说，在CASPR突变体中，光滑内质网（SER）形成细长的膜性复合物，这些复合物在节点/结旁区域积累并延伸到近结旁区域，这一缺陷与结旁结构紊乱一致。我们表明，CASPR突变体中小脑的微观组织不受影响。我们还证明，Caspr功能对于正常的CA1突触传递和可塑性并非必不可少。结合先前的研究结果，我们的结果突出表明，Caspr/Cont复合物对于轴突-胶质SJs的形成至关重要，而Cont可能独立于其与Caspr的结合来调节轴突定向和突触可塑性。
