Male germ cell-associated kinase (MAK) is required for axoneme formation during ciliogenesis in zebrafish photoreceptors

Abstract

AbstractVertebrate photoreceptors are highly specialized retinal neurons and have cilium-derived membrane organelles called outer segments (OS), 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 zebrafishmakmutants show rapid photoreceptor degeneration during embryonic development. Inmakmutants, both cone and rod photoreceptors completely lack OSs and undergo apoptosis. Interestingly, zebrafishmakmutants fail to generate axonemes during photoreceptor ciliogenesis, whereas basal bodies and transition zones are specified. These data suggest that MAK plays a specific role in axoneme development in zebrafish, in contrast to mouseMakmutants, which have elongated photoreceptor axonemes. Furthermore, the kinase activity of MAK is critical in ciliary axoneme development and photoreceptor survival. Thus, MAK is required for ciliogenesis and OS formation in zebrafish photoreceptors to ensure intracellular protein transport and photoreceptor survival.Summary statementMale germ cell-associated kinase (MAK) is a cilium-associated serine/threonine kinase that promotes axoneme development during ciliogenesis in zebrafish photoreceptors to ensure intracellular protein transport and photoreceptor survival.