Zebrafish fat-free is required for intestinal lipid absorption and Golgi apparatus structure.
The zebrafish fat-free (ffr) mutation was identified in a physiological screen for genes that regulate lipid metabolism. ffr mutant larvae are morphologically indistinguishable from wild-type sibling larvae, but their absorption of fluorescent lipids is severely impaired. Through positional cloning, we have identified a causative mutation in a highly conserved and ubiquitously expressed gene within the ffr locus. The Ffr protein contains a Dor-1 like domain typical of oligomeric Golgi complex (COG) gene, cog8. Golgi complex ultrastructure is disrupted in the ffr digestive tract. Consistent with a possible role in COG-mediated Golgi function, wild-type Ffr-GFP and COG8-mRFP fusion proteins partially colocalize in zebrafish blastomeres. Enterocyte retention of an endosomal lipid marker in ffr larvae support the idea that altered vesicle trafficking contributes to the ffr mutant defect. These data indicate that ffr is required for both Golgi structure and vesicular trafficking, and ultimately lipid transport.
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Shiu-Ying
SY
Ho
Kristin
K
Lorent
Michael
M
Pack
Steven A
SA
Farber
D000595:Amino Acid Sequence; D000818:Animals; D011992:Endosomes / Q000502:physiology; D020895:Enterocytes / Q000737:chemistry / Q000502:physiology; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006056:Golgi Apparatus / Q000737:chemistry / Q000648:ultrastructure*; D006801:Humans; D007408:Intestinal Absorption; D050356:Lipid Metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D022161:Transport Vesicles; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*
C513591:Cog8 protein, zebrafish; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D033921:Vesicular Transport Proteins; D029961:Zebrafish Proteins; C513590:vps51 protein, zebrafish