NINL and DZANK1 Co-function in Vesicle Transport and Are Essential for Photoreceptor Development in Zebrafish

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The cytoplasmic dynein 1 motor complex is known to be essential for photoreceptor outer segment formation and function. NINL, an important interaction partner of three ciliopathy-associated proteins (lebercilin, USH2A and CC2D2A), was previously shown to associate with this motor complex. In this work, we scrutinize the role of NINL using a combination of affinity proteomics and zebrafish studies, in order to gain insight into the pathogenic mechanisms underlying these three associated hereditary disorders. We identify DZANK1 as an important interaction partner of NINL and show that loss of Ninl, Dzank1, or a combination of both synergistically results in impaired transport of trans Golgi-derived vesicles and, as a consequence, defective photoreceptor outer segment formation. Using affinity proteomics, we demonstrate that NINL and DZANK1 associate with complementary subunits of the cytoplasmic dynein 1 complex. Our results support a model in which the NINL-DZANK1 protein module is essential for the proper assembly and folding of the cytoplasmic dynein 1 motor complex, shedding light on the structure and stoichiometry of this important motor complex.

Vyšlo v časopise: NINL and DZANK1 Co-function in Vesicle Transport and Are Essential for Photoreceptor Development in Zebrafish. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005574
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005574

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