| First Author | Papal S | Year | 2013 |
| Journal | Hum Mol Genet | Volume | 22 |
| Issue | 18 | Pages | 3773-88 |
| PubMed ID | 23704327 | Mgi Jnum | J:199579 |
| Mgi Id | MGI:5503249 | Doi | 10.1093/hmg/ddt228 |
| Citation | Papal S, et al. (2013) The giant spectrin betaV couples the molecular motors to phototransduction and Usher syndrome type I proteins along their trafficking route. Hum Mol Genet 22(18):3773-88 |
| abstractText | Mutations in the myosin VIIa gene cause Usher syndrome type IB (USH1B), characterized by deaf-blindness. A delay of opsin trafficking has been observed in the retinal photoreceptor cells of myosin VIIa-deficient mice. We identified spectrin betaV, the mammalian beta-heavy spectrin, as a myosin VIIa- and rhodopsin-interacting partner in photoreceptor cells. Spectrin betaV displays a polarized distribution from the Golgi apparatus to the base of the outer segment, which, unlike that of other beta spectrins, matches the trafficking route of opsin and other phototransduction proteins. Formation of spectrin betaV-rhodopsin complex could be detected in the differentiating photoreceptors as soon as their outer segment emerges. A failure of the spectrin betaV-mediated coupling between myosin VIIa and opsin molecules thus probably accounts for the opsin transport delay in myosin VIIa-deficient mice. We showed that spectrin betaV also associates with two USH1 proteins, sans (USH1G) and harmonin (USH1C). Spectrins are supposed to function as heteromers of alpha and beta subunits, but fluorescence resonance energy transfer and in vitro binding experiments indicated that spectrin betaV can also form homodimers, which likely supports its alphaII-independent betaV functions. Finally, consistent with its distribution along the connecting cilia axonemes, spectrin betaV binds to several subunits of the microtubule-based motor proteins, kinesin II and the dynein complex. We therefore suggest that spectrin betaV homomers couple some USH1 proteins, opsin and other phototransduction proteins to both actin- and microtubule-based motors, thereby contributing to their transport towards the photoreceptor outer disks. |
