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- Title
Numb Regulates the Polarized Delivery of Cyclic Nucleotide-Gated Ion Channels in Rod Photoreceptor Cilia.
- Authors
Ramamurthy, Vasanth; Jolicoeur, Christine; Koutroumbas, Demetra; Mühlhans, Johanna; Yun-Zheng Le; Hauswirth, William W.; Giessl, Andreas; Cayouette, Michel
- Abstract
The development and maintenance of protein compartmentalization is essential for neuronal function. A striking example is observed in light-sensing photoreceptors, in which the apical sensory cilium is subdivided into an inner and outer segment, each containing specific proteins essential for vision. It remains unclear, however, how such polarized protein localization is regulated. We report here that the endocytic adaptor protein Numb localizes to the inner, but not the outer segment of mouse photoreceptor cilia. Rod photoreceptor-specific inactivation of numb in vivo leads to progressive photoreceptor degeneration, indicating an essential role for Numb in photore-ceptor cell biology. Interestingly, we report that loss of Numb in photoreceptors does not affect the localization of outer segment disk membrane proteins, such as rhodopsin, Peripherin-rds, Rom-1, and Abca4, but significantly disrupts the localization of the rod cyclic nucleotide-gated (Cng) channels, which accumulates on the inner segment plasma membrane in addition to its normal localization to the outer segments. Mechanistically, we show that Numb interacts with both subunits of the Cng channel and promotes the trafficking of Cnga1 to the recycling endosome. These results suggest a model in which Numb prevents targeting of Cng channels to the inner segment, by promoting their trafficking through the recycling endosome, where they can be sorted for specific delivery to the outer segment. This study uncovers a novel mechanism regulating polarized protein delivery in light-sensing cilia, raising the possibility that Numb plays a part in the regulation of protein trafficking in other types of cilia.
- Subjects
CYCLIC nucleotide-gated ion channels; RETINAL rod photoreceptor cells; CILIARY body; ENDOSOMES; CALCIUM channels; CLATHRIN
- Publication
Journal of Neuroscience, 2014, Vol 34, Issue 42, p13976
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1938-14.2014