PDF(Pubmed)
Abstract：
Vertebrate photoreceptors are highly specialized retinal neurons that have cilium-derived membrane organelles called outer segments, which function as platforms for phototransduction. Male germ cell-associated kinase (MAK) is a cilium-associated serine/threonine kinase, and its genetic mutation causes photoreceptor degeneration in mice and retinitis pigmentosa in humans. However, the role of MAK in photoreceptors is not fully understood. Here, we report that zebrafish mak mutants show rapid photoreceptor degeneration during embryonic development. In mak mutants, both cone and rod photoreceptors completely lacked outer segments and underwent apoptosis. Interestingly, zebrafish mak mutants failed to generate axonemes during photoreceptor ciliogenesis, whereas basal bodies were specified. These data suggest that Mak contributes to axoneme development in zebrafish, in contrast to mouse Mak mutants, which have elongated photoreceptor axonemes. Furthermore, the kinase activity of Mak was found to be critical in ciliary axoneme development and photoreceptor survival. Thus, Mak is required for ciliogenesis and outer segment formation in zebrafish photoreceptors to ensure intracellular protein transport and photoreceptor survival.
摘要：
脊椎动物光感受器是高度特化的视网膜神经元，具有称为外节（OS）的纤毛衍生膜细胞器，作为光转导的平台。男性生殖细胞相关激酶（MAK）是纤毛相关的丝氨酸/苏氨酸激酶，它的基因突变导致小鼠的光感受器变性和人类的视网膜色素变性。然而,MAK在光感受器中的作用尚未完全了解。这里,我们报告说，斑马鱼mak突变体在胚胎发育过程中表现出快速的光感受器变性。在mak突变体中，视锥和视杆光感受器都完全缺乏OS并发生凋亡。有趣的是,斑马鱼mak突变体在光感受器纤毛发生过程中无法产生轴突，而基底是指定的。这些数据表明MAK有助于斑马鱼的轴突发育，与小鼠Mak突变体相比，有细长的感光轴突。此外，MAK的激酶活性在睫状轴突发育和光感受器存活中至关重要。因此，MAK是斑马鱼光感受器中纤毛发生和OS形成所必需的，以确保细胞内蛋白质转运和光感受器存活。
