title: Essential role of RGS-PX1/sorting nexin 13 in mouse development and regulation of endocytosis dynamics.
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.
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093-0651, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zheng
authors.forename: Tingdong
authors.initials: T
authors.lastname: Tang
authors.forename: Nan
authors.initials: N
authors.lastname: Tang
authors.forename: Krystyna
authors.initials: K
authors.lastname: Kudlicka
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Ohtsubo
authors.forename: Phuong
authors.initials: P
authors.lastname: Ma
authors.forename: Jamey D
authors.initials: JD
authors.lastname: Marth
authors.forename: Marilyn G
authors.initials: MG
authors.lastname: Farquhar
authors.forename: Eero
authors.initials: E
authors.lastname: Lehtonen
mesh_terms: D000818:Animals; D001343:Autophagy; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D004247:DNA / Q000235:genetics; D047108:Embryonic Development / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000473:pathology; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology; D018390:Gene Targeting; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D009436:Neural Tube Defects / Q000209:etiology; D010920:Placenta / Q000002:abnormalities; D011247:Pregnancy; D058305:Sorting Nexins; D014617:Vacuoles / Q000473:pathology; D033921:Vesicular Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; D004247:DNA