Characterization of the Drosophila ortholog of the human Usher Syndrome type 1G protein sans.
BACKGROUND
The Usher syndrome (USH) is the most frequent deaf-blindness hereditary disease in humans. Deafness is attributed to the disorganization of stereocilia in the inner ear. USH1, the most severe subtype, is associated with mutations in genes encoding myosin VIIa, harmonin, cadherin 23, protocadherin 15, and sans. Myosin VIIa, harmonin, cadherin 23, and protocadherin 15 physically interact in vitro and localize to stereocilia tips in vivo, indicating that they form functional complexes. Sans, in contrast, localizes to vesicle-like structures beneath the apical membrane of stereocilia-displaying hair cells. How mutations in sans result in deafness and blindness is not well understood. Orthologs of myosin VIIa and protocadherin 15 have been identified in Drosophila melanogaster and their genetic analysis has identified essential roles in auditory perception and microvilli morphogenesis, respectively.


RESULTS
Here, we have identified and characterized the Drosophila ortholog of human sans. Drosophila Sans is expressed in tubular organs of the embryo, in lens-secreting cone cells of the adult eye, and in microvilli-displaying follicle cells during oogenesis. Sans mutants are viable, fertile, and mutant follicle cells appear to form microvilli, indicating that Sans is dispensable for fly development and microvilli morphogenesis in the follicle epithelium. In follicle cells, Sans protein localizes, similar to its vertebrate ortholog, to intracellular punctate structures, which we have identified as early endosomes associated with the syntaxin Avalanche.


CONCLUSIONS
Our work is consistent with an evolutionary conserved function of Sans in vesicle trafficking. Furthermore it provides a significant basis for further understanding of the role of this Usher syndrome ortholog in development and disease.
Demontis
Fabio
F
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Dahmann
Christian
C
D000818:Animals; D017089:Ankyrin Repeat; D003001:Cloning, Molecular; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D005123:Eye / Q000166:cytology / Q000378:metabolism; D005260:Female; D005298:Fertility; D006801:Humans; D000081412:Myosin VIIa; D009218:Myosins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D006080:Ovarian Follicle / Q000166:cytology / Q000378:metabolism*; D010802:Phylogeny; D050765:Qa-SNARE Proteins / Q000378:metabolism
D029721:Drosophila Proteins; C000631455:MYO7A protein, human; D000081412:Myosin VIIa; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; C477452:USH1G protein, human; C514773:ck protein, Drosophila; C000631458:myosin 7a, Drosophila; D009218:Myosins