Manavalan Mary Ann, Jayasinghe Vatsala Ruvini, Grewal Rickinder, Bhat Krishna Moorthi
Department of Neuroscience and Cell Biology, University of Texas Medical Branch School of Medicine, Galveston, TX 77555, USA.
Sci Signal. 2017 Jun 20;10(484):eaam5841. doi: 10.1126/scisignal.aam5841.
Slit proteins act as repulsive axon guidance cues by activating receptors of the Roundabout (Robo) family. During early neurogenesis in , Slit prevents the growth cones of longitudinal tract neurons from inappropriately crossing the midline, thus restricting these cells to trajectories parallel to the midline. Slit is expressed in midline glial cells, and Robo is present in longitudinal axon tracts and growth cones. We showed that the enzyme Mummy (Mmy) controlled Slit-Robo signaling through mechanisms that affected both the ligand and the receptor. Mmy was required for the glycosylation of Slit, which was essential for Slit secretion. Mmy was also required for maintaining the abundance and spatial distribution of Robo through an indirect mechanism that was independent of Slit secretion. Moreover, secretion of Slit was required to maintain the fasciculation and position of longitudinal axon tracts, thus maintaining the hardwiring of the nervous system. Thus, Mmy is required for Slit secretion and for maintaining Robo abundance and distribution in the developing nervous system in .
Slit蛋白通过激活Roundabout(Robo)家族的受体,作为轴突导向排斥信号。在早期神经发生过程中,Slit可防止纵向神经束神经元的生长锥不恰当地越过中线,从而将这些细胞限制在与中线平行的轨迹上。Slit在中线神经胶质细胞中表达,而Robo存在于纵向轴突束和生长锥中。我们发现,Mummy(Mmy)酶通过影响配体和受体的机制来控制Slit-Robo信号传导。Mmy是Slit糖基化所必需的,而糖基化对于Slit的分泌至关重要。Mmy还通过一种独立于Slit分泌的间接机制来维持Robo的丰度和空间分布。此外,Slit的分泌对于维持纵向轴突束的成束和位置是必需的,从而维持神经系统的布线。因此,在[具体物种]发育中的神经系统中,Mmy对于Slit的分泌以及维持Robo的丰度和分布是必需的。