Drosophila Tempura, a novel protein prenyltransferase α subunit, regulates notch signaling via Rab1 and Rab11.
Vesicular trafficking plays a key role in tuning the activity of Notch signaling. Here, we describe a novel and conserved Rab geranylgeranyltransferase (RabGGT)-α-like subunit that is required for Notch signaling-mediated lateral inhibition and cell fate determination of external sensory organs. This protein is encoded by tempura, and its loss affects the secretion of Scabrous and Delta, two proteins required for proper Notch signaling. We show that Tempura forms a heretofore uncharacterized RabGGT complex that geranylgeranylates Rab1 and Rab11. This geranylgeranylation is required for their proper subcellular localization. A partial dysfunction of Rab1 affects Scabrous and Delta in the secretory pathway. In addition, a partial loss Rab11 affects trafficking of Delta. In summary, Tempura functions as a new geranylgeranyltransferase that regulates the subcellular localization of Rab1 and Rab11, which in turn regulate trafficking of Scabrous and Delta, thereby affecting Notch signaling.
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America.
Wu-Lin
WL
Charng
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America ; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America ; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas, United States of America.
Shinya
S
Yamamoto
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America ; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, United States of America.
Manish
M
Jaiswal
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America ; Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas, United States of America.
Vafa
V
Bayat
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America.
Bo
B
Xiong
Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.
Ke
K
Zhang
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
Hector
H
Sandoval
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America.
Gabriela
G
David
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
Stephen
S
Gibbs
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America.
Hsiang-Chih
HC
Lu
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America.
Kuchuan
K
Chen
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America ; Department of Neurology, Baylor College of Medicine, Houston, Texas, United States of America.
Nikos
N
Giagtzoglou
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America ; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America ; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas, United States of America ; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, United States of America ; Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas, United States of America ; Department of Neuroscience, Baylor College of Medicine, Houston, Texas, United States of America.
Hugo J
HJ
Bellen
D000818:Animals; D004122:Dimethylallyltranstransferase / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D017368:Protein Prenylation; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000235:genetics* / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020761:rab1 GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
D004122:Dimethylallyltranstransferase; D029721:Drosophila Proteins; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D021122:Protein Subunits; D051880:Receptors, Notch; D020691:rab GTP-Binding Proteins; D020761:rab1 GTP-Binding Proteins; C497759:N protein, Drosophila; C064045:delta protein; C066579:sca protein, Drosophila; C559123:Rab11 protein, Drosophila; D000099193:rab11 GTP-Binding Proteins