Developmental Neurobiology Unit, Okinawa Institute of Science and Technology Graduate University, Tancha, Okinawa 904-0495, Japan.
Dis Model Mech. 2024 Jul 1;17(7). doi: 10.1242/dmm.050618. Epub 2024 Jul 16.
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.
脊椎动物光感受器是高度特化的视网膜神经元，具有纤毛衍生的膜细胞器，称为外节，其作为光转导的平台发挥作用。 精子细胞相关激酶（MAK）是一种纤毛相关的丝氨酸/苏氨酸激酶，其基因突变导致小鼠的光感受器变性和人类的色素性视网膜炎。 然而，MAK 在光感受器中的作用尚不完全清楚。 在这里，我们报告斑马鱼 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完全缺乏外节，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未能产生轴丝，而基底体被指定。 这些数据表明 Mak 有助于斑马鱼轴丝的发育，与具有延长的光感受器轴丝的小鼠 Mak 突变体形成对比。 此外，发现 Mak 的激酶活性对于纤毛轴丝的发育和光感受器的存活至关重要。 因此，Mak 是斑马鱼光感受器纤毛发生和外节形成所必需的，以确保细胞内蛋白质运输和光感受器的存活。
