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N. L. Overlack, D. Kilic, T. Maerker, K. Bauss, E. van Wijk, G. Stern-Schneider, R. Roepman, H. Kremer, U. Wolfrum; USH1G Protein Sans Interacts With Myomegalin in Mammalian Photoreceptor Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1096.
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© ARVO (1962-2015); The Authors (2016-present)
The human Usher syndrome (USH) is the most common form of combined deaf-blindness. Usher type I (USH1), the most severe form, is characterized by profound congenital deafness, constant vestibular dysfunction and pre-pubertal onset of retinitis pigmentosa. USH1g encodes the SANS (scaffold protein containing ankyrin repeats and SAM domain) protein which contains putative protein-binding motifs. Recent studies revealed SANS scaffolding function in the protein interactome related to USH. The aim of the study was to enlighten SANS cellular functions by identifying novel interaction partners of SANS.
Y2H screen of retinal cDNA libraries were performed with the central domain of SANS. Expression analyses were assessed by RT-PCR and Western blots. Protein-protein interactions were validated by GST pull-down. Indirect immunofluorescence assessed co-localization of identified partners in cell culture and mouse, macaque as well as human retinas.
The phosphodiesterase 4D interacting protein Myomegalin (PDE4DIP) was identified and confirmed as an interaction partner of the USH1G protein SANS. Myomegalin is expressed in a variety of tissues including the murine, macaque and human retina. In retinas Myomegalin is localized in the RPE, photoreceptors, inner nuclear layer and ganglion cell layer. Co-localization of SANS and Myomegalin was found in the ciliary region and the inner segment of photoreceptor cells. Co-localization of both interacting partners at centrosomes and spindle poles of cultured cells confirmed their microtubule association.
Myomegalin directly interacts with the USH1g protein SANS and integrates Myomegalin in the multifunctional protein interactome related to USH. Localization of both proteins at microtubule enriched compartments suggests a microtubule-associated function. A role of the SANS-Myomegalin complex in microtubule-dependent inner segment cargo transport towards the ciliary apparatus of photoreceptor cells is proposed.
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