title: 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.affiliation: Institut Pasteur, Unité de génétique et physiologie de l'audition, Paris, France.
authors.forename: Samantha
authors.initials: S
authors.lastname: Papal
authors.forename: Matteo
authors.initials: M
authors.lastname: Cortese
authors.forename: Kirian
authors.initials: K
authors.lastname: Legendre
authors.forename: Nasrin
authors.initials: N
authors.lastname: Sorusch
authors.forename: Joseph
authors.initials: J
authors.lastname: Dragavon
authors.forename: Iman
authors.initials: I
authors.lastname: Sahly
authors.forename: Spencer
authors.initials: S
authors.lastname: Shorte
authors.forename: Uwe
authors.initials: U
authors.lastname: Wolfrum
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
authors.forename: Aziz
authors.initials: A
authors.lastname: El-Amraoui
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D006367:HeLa Cells; D006801:Humans; D055537:Light Signal Transduction; D051379:Mice; D008868:Microtubule Proteins / Q000378:metabolism; D000081412:Myosin VIIa; D009218:Myosins / Q000378:metabolism*; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D012243:Rhodopsin / Q000378:metabolism; D013049:Spectrin / Q000235:genetics* / Q000378:metabolism*; D052245:Usher Syndromes / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C000631455:MYO7A protein, human; D008868:Microtubule Proteins; C000631456:Myo7a protein, mouse; D000081412:Myosin VIIa; C118970:USH1C protein, human; D013049:Spectrin; D012243:Rhodopsin; D009218:Myosins