Article ; Online: The Cdc42-interacting protein-4 (CIP4) gene knock-out mouse reveals delayed and decreased endocytosis.
The Journal of biological chemistry
2009 Volume 285, Issue 7, Page(s) 4348–4354
Abstract: 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 ... ...
| Abstract | 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. |
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| MeSH term(s) | Adipocytes/metabolism ; Animals ; Biological Transport/genetics ; Biological Transport/physiology ; Blotting, Southern ; Blotting, Western ; Cattle ; Cells, Cultured ; Endocytosis/genetics ; Endocytosis/physiology ; Female ; Genotype ; Glucose/metabolism ; Glucose Transporter Type 4/genetics ; Glucose Transporter Type 4/metabolism ; Male ; Mice ; Mice, Inbred ICR ; Mice, Knockout ; Microscopy, Fluorescence ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/metabolism ; Minor Histocompatibility Antigens ; Reverse Transcriptase Polymerase Chain Reaction ; Transferrin/metabolism |
| Chemical Substances | Glucose Transporter Type 4 ; Microtubule-Associated Proteins ; Minor Histocompatibility Antigens ; Slc2a4 protein, mouse ; Transferrin ; Trip10 protein, mouse ; Glucose (IY9XDZ35W2) |
| Language | English |
| Publishing date | 2009-11-17 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2997-x |
| ISSN | 1083-351X ; 0021-9258 |
| ISSN (online) | 1083-351X |
| ISSN | 0021-9258 |
| DOI | 10.1074/jbc.M109.041038 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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