The Cdc42-interacting protein-4 (CIP4) gene knock-out mouse reveals delayed and decreased endocytosis.
The newly described F-BAR (Fer/CIP4 and Bin, amphiphysin, Rvs) family of proteins includes Cdc42-interacting protein-4 (CIP4), formin-binding protein-17 (FBP-17) and transactivator of cytoskeletal assembly-1 (Toca-1), and drives membrane deformation and invagination. Membrane remodeling affects endocytosis, vesicle budding, and cargo selection. The F-BAR family presents a novel family of proteins, which little is known about their in vivo function. We investigated the physiological role of CIP4, by creating Cip4-null mice through homologous recombination. Compared with their wild-type littermates, the Cip4-null mice displayed lower early post-prandial glucose levels. Adipocytes isolated from Cip4-null mice exhibited increased [(14)C]2-deoxyglucose uptake compared with cells from wild-type mice. The enhanced insulin sensitivity was not due to higher levels of insulin or phospho-Akt, a critical player in insulin signaling. However, higher glucose transporter 4 (GLUT4) levels were detected in muscle membrane fractions in Cip4-null mice under insulin stimulation. Mouse embryonic fibroblasts from Cip4-null mice demonstrated decreased transferrin uptake, fluorescein isothiocyanate-dextran, and horseradish peroxidase uptake, indicating that CIP4 affects multiple modes of endocytosis. These studies demonstrate a physiological role for CIP4 in endocytosis leading to a whole animal phenotype.
Feng
Yanming
Y
Division of Pediatrics, University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA.
Hartig
Sean M
SM
Bechill
John E
JE
Blanchard
Elisabeth G
EG
Caudell
Eva
E
Corey
Seth J
SJ
D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D015139:Blotting, Southern; D015153:Blotting, Western; D002417:Cattle; D002478:Cells, Cultured; D004705:Endocytosis / Q000235:genetics / Q000502:physiology*; D005260:Female; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014168:Transferrin / Q000378:metabolism
D051275:Glucose Transporter Type 4; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; C495693:Slc2a4 protein, mouse; D014168:Transferrin; C485787:Trip10 protein, mouse; D005947:Glucose