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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Zheng, Bin Tang, Nan Farquhar, Marilyn G. Ohtsubo, Kazuaki Marth, Jamey D. Ma, Phuong Kudlicka, Krystyna Lehtonen, Eero Tang, Tingdong |
| Description | Author Affiliation: Zheng B ( Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093-0651, USA.); |
| Abstract | RGS-PX1 (also known as sorting nexin 13) is a member of both the regulator of G protein signaling (RGS) and sorting nexin (SNX) protein families. Biochemical and cell culture studies have shown that RGS-PX1/SNX13 attenuates Galphas-mediated signaling through its RGS domain and regulates endocytic trafficking and degradation of the epidermal growth factor receptor. To understand the functions of RGS-PX1/SNX13 in vivo, we generated mice carrying targeted mutations of Snx13 and found that systemic Snx13-null mice were embryonic lethal around midgestation. Snx13-null embryos had significant overall growth retardation and defects in neural tube closure, blood vessel formation, and the formation of the placental labyrinthine layer. Moreover, the Snx13-null visceral yolk sac endoderm cells showed dramatic changes in the organization of endocytic compartments, abundant autophagic vacuoles, and abnormal localization of several endocytic markers, including megalin, a receptor for nutrients and proteins; ARH, a coat protein that binds megalin; LAMP2; and LC3. These changes suggest that Snx13-null embryos are defective in nutrient uptake and transport, which may contribute to the other developmental abnormalities observed. Taken together, our findings demonstrate an essential role for RGS-PX1/SNX13 in mouse development and provide previously undescribed insights into its cellular function in the regulation of endocytosis dynamics. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 45 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Carrier Proteins Physiology Embryonic Development Endocytosis Vesicular Transport Proteins Animals Autophagy Genetics DNA Endosomes Pathology Fetal Growth Retardation Etiology Gene Targeting Mice Mice, Inbred C57BL Mice, Knockout Neovascularization, Physiologic Neural Tube Defects Placenta Abnormalities Pregnancy Sorting Nexins Vacuoles Deficiency Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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