The giant spectrin βV couples the molecular motors to phototransduction and Usher syndrome type I proteins along their trafficking route.

Abstract

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 βV, the mammalian β-heavy spectrin, as a myosin VIIa- and rhodopsin-interacting partner in photoreceptor cells. Spectrin βV displays a polarized distribution from the Golgi apparatus to the base of the outer segment, which, unlike that of other β spectrins, matches the trafficking route of opsin and other phototransduction proteins. Formation of spectrin βV-rhodopsin complex could be detected in the differentiating photoreceptors as soon as their outer segment emerges. A failure of the spectrin βV-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 βV also associates with two USH1 proteins, sans (USH1G) and harmonin (USH1C). Spectrins are supposed to function as heteromers of α and β subunits, but fluorescence resonance energy transfer and in vitro binding experiments indicated that spectrin βV can also form homodimers, which likely supports its αII-independent βV functions. Finally, consistent with its distribution along the connecting cilia axonemes, spectrin βV binds to several subunits of the microtubule-based motor proteins, kinesin II and the dynein complex. We therefore suggest that spectrin βV 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.

• Authors: Samantha Papal, Matteo Cortese, Kirian Legendre, Nasrin Sorusch, Joseph Dragavon, Iman Sahly, Spencer Shorte, Uwe Wolfrum, Christine Petit, Aziz El-Amraoui
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 22 Issue 18 Pg. 3773-88 (Sep 15 2013) ISSN: 1460-2083 [Electronic] England
• PMID: 23704327 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Cell Cycle Proteins
• Cytoskeletal Proteins
• MYO7A protein, human
• Microtubule Proteins
• Myo7a protein, mouse
• Myosin VIIa
• USH1C protein, human
• Spectrin
• Rhodopsin
• Myosins

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Animals
• Cell Cycle Proteins
• Cytoskeletal Proteins
• HeLa Cells
• Humans
• Light Signal Transduction
• Mice
• Microtubule Proteins (metabolism)
• Myosin VIIa
• Myosins (metabolism)
• Photoreceptor Cells, Vertebrate (metabolism)
• Retina (metabolism)
• Rhodopsin (metabolism)
• Spectrin (genetics, metabolism)
• Usher Syndromes (metabolism)