RRC ID 46752
Author Matsui T, Itoh T, Fukuda M.
Title Small GTPase Rab12 regulates constitutive degradation of transferrin receptor.
Journal Traffic
Abstract Transferrin receptor (TfR) is a well-characterized plasma membrane protein that travels between the plasma membrane and intracellular membrane compartments. Although TfR itself should undergo degradation, the same as other intracellular proteins, whether a specific TfR degradation pathway exists has never been investigated. In this study, we screened small GTPase Rab proteins, common regulators of membrane traffic in all eukaryotes, for proteins that are specifically involved in TfR degradation. We performed the screening by three sequential methods, i.e. colocalization of Rab with TfR, colocalization with lysosomes, and knockdown of Rab by specific small interfering RNA (siRNA), and succeeded in identifying Rab12, a previously uncharacterized Rab isoform, as a prime candidate among the 60 human or mouse Rabs screened. We showed that expression of a constitutive active mutant of Rab12 reduced the amount of TfR protein, whereas functional ablation of Rab12 by knockdown of either Rab12 itself or its upstream activator Dennd3 increased the amount of TfR protein. Interestingly, however, knockdown of Rab12 had no effect on the degradation of epidermal growth factor receptor (EGFR) protein, i.e. on a conventional degradation pathway. Our findings indicated that TfR is constitutively degraded by a Rab12-dependent pathway (presumably from recycling endosomes to lysosomes), which is independent of the conventional degradation pathway.
Volume 12(10)
Pages 1432-43
Published 2011-10-1
DOI 10.1111/j.1600-0854.2011.01240.x
PMID 21718402
MeSH Animals COS Cells Cell Line, Tumor Cell Membrane / metabolism Chlorocebus aethiops Electrophoresis, Polyacrylamide Gel Humans Intracellular Membranes / metabolism Mice Models, Biological Protein Transport RNA, Small Interfering / genetics Receptors, Transferrin / metabolism* Spleen / metabolism Transfection rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / metabolism rab GTP-Binding Proteins / physiology*
IF 3.951
Times Cited 53
DNA material pEGFP-C1-Rab40 (RDB14338) pEGFP-C1-Rab1B (RDB17237) pEGFP-C1-Rab2B (RDB17239) pEGFP-C1-Rab3B (RDB17241) pEGFP-C1-Rab3C (RDB17242) pEGFP-C1-Rab3D (RDB17243) pEGFP-C1-Rab4B (RDB17245) pEGFP-C1-Rab5B (RDB17247) pEGFP-C1-Rab5C (RDB17248) pEGFP-C1-Rab6B (RDB17250) pEGFP-C1-Rab6C (RDB17251) pEGFP-C1-Rab8B (RDB17254) pEGFP-C1-Rab9B (RDB17256) pEGFP-C1-Rab11B (RDB17258) pEGFP-C1-Rab22B (RDB17268) pEGFP-C1-Rab27B (RDB17274) pEGFP-C1-Rab39B (RDB17283) pEGFP-C1-Rab40B (RDB17285) pEGFP-C1-Rab42 (RDB17286) pEGFP-C1-Rab43 (RDB17287)
Human and Animal Cells NB2a(RCB2639) COS-7(RCB0539)