title: Crag is a GEF for Rab11 required for rhodopsin trafficking and maintenance of adult photoreceptor cells.
abstract: Rhodopsins (Rhs) are light sensors, and Rh1 is the major Rh in the Drosophila photoreceptor rhabdomere membrane. Upon photoactivation, a fraction of Rh1 is internalized and degraded, but it remains unclear how the rhabdomeric Rh1 pool is replenished and what molecular players are involved. Here, we show that Crag, a DENN protein, is a guanine nucleotide exchange factor for Rab11 that is required for the homeostasis of Rh1 upon light exposure. The absence of Crag causes a light-induced accumulation of cytoplasmic Rh1, and loss of Crag or Rab11 leads to a similar photoreceptor degeneration in adult flies. Furthermore, the defects associated with loss of Crag can be partially rescued with a constitutive active form of Rab11. We propose that upon light stimulation, Crag is required for trafficking of Rh from the trans-Golgi network to rhabdomere membranes via a Rab11-dependent vesicular transport.
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiong
authors.forename: Vafa
authors.initials: V
authors.lastname: Bayat
authors.forename: Manish
authors.initials: M
authors.lastname: Jaiswal
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.forename: Hector
authors.initials: H
authors.lastname: Sandoval
authors.forename: Wu-Lin
authors.initials: WL
authors.lastname: Charng
authors.forename: Tongchao
authors.initials: T
authors.lastname: Li
authors.forename: Gabriela
authors.initials: G
authors.lastname: David
authors.forename: Lita
authors.initials: L
authors.lastname: Duraine
authors.forename: Yong-Qi
authors.initials: YQ
authors.lastname: Lin
authors.forename: G Gregory
authors.initials: GG
authors.lastname: Neely
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Hugo J
authors.initials: HJ
authors.lastname: Bellen
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism / Q000528:radiation effects; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D004596:Electroretinography; D005260:Female; D055785:Gene Knockdown Techniques; D017344:Genes, Insect / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D008027:Light; D008297:Male; D009154:Mutation / Q000235:genetics; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects / Q000648:ultrastructure; D011485:Protein Binding / Q000528:radiation effects; D021381:Protein Transport / Q000528:radiation effects; D012162:Retinal Degeneration / Q000473:pathology / Q000503:physiopathology; D012243:Rhodopsin / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D029721:Drosophila Proteins; D020662:Guanine Nucleotide Exchange Factors; D012243:Rhodopsin; D020691:rab GTP-Binding Proteins; C581135:Crag protein, Drosophila; C083315:ninaE protein, Drosophila; C559123:Rab11 protein, Drosophila; D000099193:rab11 GTP-Binding Proteins