Mechanism of positioning the cell nucleus in vertebrate photoreceptors

Organelles are frequently distributed in a nonrandom manner in a cell's cytoplasm. A particular distribution pattern often facilitates a specific function of a cell, whereas its aberrations can lead to cell death. We show that a mutation in the zebrafish mikre oko (mok) locus, which encodes dynactin 1 subunit of the dynactin complex, produces a severe displacement of the photoreceptor cell nucleus toward the synaptic terminus. Interference with the function of other dynein complex constituents, including p50/dynamitin, the Lis1 polypeptide, and the disruption of a nuclear envelope component of the syne gene family in vertebrate photoreceptors also result in the mispositioning of nuclei. Although the overall photoreceptor polarity is not affected, this phenotype is accompanied by a misdistribution of the Bardet-Biedl syndrome 4 polypeptide and a decreased photoreceptor survival. These findings reveal an important mechanism that regulates nuclear position in vertebrate neurons.