Mutations in the Dynein1 Complex are Permissible for Basal Body Migration in Photoreceptors but Alter Rab6 Localization

Abstract

The photoreceptor outer segment is a specialized primary cilium, and anchoring of the basal body at the apical membrane is required for outer segment formation. We hypothesized that basal body localization and outer segment formation would require the microtubule motor dynein 1 and analyzed the zebrafish cannonball and mike oko mutants, which carry mutations in the heavy chain subunit of cytoplasmic dynein 1 (dync1h1) and the p150Glued subunit of Dynactin (dctn1a). The distribution of Rab6, a player in the post-Golgi trafficking of rhodopsin, was also examined. Basal body docking was unaffected in both mutants, but Rab6 expression was reduced. The results suggest that dynein 1 is dispensable for basal body docking but that outer segment defects may be due to defects in post-Golgi trafficking.

Effect of conditional deletion of cytoplasmic dynein heavy chain DYNC1H1 on postnatal photoreceptors

“…Interestingly, a few mother centrioles (basal bodies) appear to be able to engage in ciliogenesis and form diminutive membrane OS-like structures filled with PDE6. In zebrafish cnb and mok mutants, basal body docking was unaffected supporting this result [ 46 ]. As MOE antibody recognizes both rod and cone PDE6 it is not possible to distinguish rod and cone OS, but based on structural integrity of cones ( Fig 6 ) we interpret these structures to originate from cones.…”

Ocular Ciliopathies: Genetic and Mechanistic Insights into Developing Therapies

“…The loss of the distal tips is compensated by the simultaneous addition of new discs and membranes at the base of the outer segment. Both the shedding and renewal of the outer segment exhibit stringent circadian regulation; (iii) The involvement of the retrograde movement of the cargo mediated by cytoplasmic dynein in photoreceptor cilia is unclear [21, 26–27]. Recent studies though have indicated that the retrograde movement may involve recycling of the IFT proteins rather than of a cargo [26–27].…”

“…Both the shedding and renewal of the outer segment exhibit stringent circadian regulation; (iii) The involvement of the retrograde movement of the cargo mediated by cytoplasmic dynein in photoreceptor cilia is unclear [21, 26–27]. Recent studies though have indicated that the retrograde movement may involve recycling of the IFT proteins rather than of a cargo [26–27]. Thus, disruption of the retrograde machinery may affect photoreceptor ciliary formation and maintenance, which may lead to eventual ciliary dysfunction and photoreceptor degeneration.…”