PDF(Pubmed)
Abstract：
The vesicle-associated membrane protein 7 (VAMP7) is a SNARE protein of the longin family involved in a wide range of subcellular trafficking events, including neurite sprouting and elongation. The expression of the human gene SYBL1, encoding VAMP7, is finely regulated by alternative splicing. Among the minor isoforms identified so far, VAMP7j is the one most expressed and modulated in the human brain. Therefore, we focused on gaining functional evidence on VAMP7j, which lacks a functional SNARE motif but retains both the longin and transmembrane domains. In human SH-SY5Y cells, we found VAMP7j to modulate neuritogenesis by mediating transport of L1CAM toward the plasma membrane, in a fashion regulated by phosphorylation of the longin domain. VAMP7-mediated regulation of L1CAM trafficking seems at least to differentiate humans from rats, with VAMP7j CNS expression being restricted to primates, including humans. Since L1CAM is a central player in neuritogenesis and axon guidance, these findings suggest the species-specific splicing of SYBL1 is among the fine tuners of human neurodevelopmental complexity.
摘要：
囊泡相关膜蛋白7（VAMP7）是longin家族的SNARE蛋白，参与各种亚细胞运输事件，包括神经突发芽和伸长。编码VAMP7的人基因SYBL1的表达受到可变剪接的精细调节。在迄今为止发现的次要同工型中，VAMP7j是在人脑中表达和调节最多的一种。因此,我们专注于获得关于VAMP7j的功能证据，缺乏功能性SNARE基序，但保留了longin和跨膜结构域。在人SH-SY5Y细胞中，我们发现VAMP7j通过介导L1CAM向质膜的转运来调节神经生成，以一种由长蛋白结构域磷酸化调节的方式。VAMP7介导的L1CAM贩运调节似乎至少可以区分人类和大鼠，VAMP7jCNS表达仅限于灵长类动物，包括人类。由于L1CAM是神经生成和轴突引导的核心角色，这些发现表明SYBL1的物种特异性剪接是人类神经发育复杂性的微调之一。
