Lightoid and Claret: a rab GTPase and its putative guanine nucleotide exchange factor in biogenesis of Drosophila eye pigment granules.
To elucidate the biogenetic pathways for the generation of lysosome-related organelles, we have chosen to study the Drosophila eye pigment granules because they are lysosome-related and the fruit fly provides the advantages of a genetic system in which many mutations affect eye color. Here, we report the molecular identification of two classic Drosophila eye-color genes required for pigment granule biogenesis, claret and lightoid; the former encodes a protein containing seven repeats with sequence similarity to those that characterize regulator of chromosome condensation 1 (RCC1, a guanine nucleotide exchange factor for the small GTPase, Ran), and the latter encodes a rab GTPase, Rab-RP1. We demonstrate in transfected cells that Claret, through its RCC1-like domain, interacts preferentially with the nucleotide-free form of Rab-RP1, and this interaction involves Claret's first three RCC1-like repeats that are also critical for Claret's function in pigment granule biogenesis in transgenic rescue experiments. In addition, double-mutant analyses suggest that the gene products of claret and lightoid function in the same pathway, which is different from that of garnet and ruby (which encode the delta- and beta-subunit of the tetrameric adaptor protein 3 complex, respectively). Taken together, our results suggest that Claret functions as a guanine nucleotide exchange factor for Lightoid/Rab-RP1 in an adaptor protein 3-independent vesicular trafficking pathway of pigment granule biogenesis.
Ma
Jinping
J
Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
Plesken
Heide
H
Treisman
Jessica E
JE
Edelman-Novemsky
Irit
I
Ren
Mindong
M
D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins; D022162:Cytoplasmic Vesicles / Q000737:chemistry*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology; D020558:GTP Phosphohydrolases; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000502:physiology*; D008247:Lysosomes / Q000737:chemistry; D009687:Nuclear Proteins; D011485:Protein Binding; D012168:Retinal Pigments / Q000096:biosynthesis*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; D012168:Retinal Pigments; D020558:GTP Phosphohydrolases; C471560:Rab32 protein, Drosophila; D020691:rab GTP-Binding Proteins