期刊
JOURNAL OF CELL SCIENCE
卷 128, 期 24, 页码 4588-4600出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.175075
关键词
GGA2; Glut4 trafficking; Actin; Clathrin
类别
资金
- European Research Council [242820]
- Academy of Finland [131255, 218021, 255551, 134379]
- Sigrid Juselius Foundation
- Paivikki and Sakari Sohlberg Foundation
- Diabetes Research Foundation
- Faculty of Medicine, University of Helsinki
- Doctoral Programme in Biomedicine
- Academy of Finland (AKA) [255551, 255551] Funding Source: Academy of Finland (AKA)
The adapter protein CD2-associated protein (CD2AP) functions in various signaling and vesicle trafficking pathways, including endosomal sorting and/or trafficking and degradation pathways. Here, we investigated the role of CD2AP in insulin-dependent glucose transporter 4 (Glut4, also known as SLC2A4) trafficking and glucose uptake. Glucose uptake was attenuated in CD2AP(-/-) podocytes compared with wild-type podocytes in the basal state, and CD2AP(-/-) podocytes failed to increase glucose uptake in response to insulin. Live-cell imaging revealed dynamic trafficking of HA-Glut4-GFP in wild-type podocytes, whereas in CD2AP(-/-) podocytes, HA-Glut4-GFP clustered perinuclearly. In subcellular membrane fractionations, CD2AP co-fractionated with Glut4, IRAP (also known as LNPEP) and sortilin, constituents of Glut4 storage vesicles (GSVs). We further found that CD2AP forms a complex with GGA2, a clathrin adaptor, which sorts Glut4 to GSVs, suggesting a role for CD2AP in this process. We also found that CD2AP forms a complex with clathrin and connects clathrin to actin in the perinuclear region. Furthermore, clathrin recycling back to trans-Golgi membranes from the vesicular fraction containing GSVs was defective in the absence of CD2AP. This leads to reduced insulin-stimulated trafficking of GSVs and attenuated glucose uptake into CD2AP(-/-) podocytes.
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