足细胞
mTORC1型
细胞生物学
蛋白激酶B
磷酸化
胞饮病
PI3K/AKT/mTOR通路
内吞作用
生物
信号转导
化学
细胞
肾
内分泌学
生物化学
蛋白尿
作者
Rui Hua,Mauricio Torres,Jinzi Wei,Xiaowei Sun,Li Wang,Ken Inoki,Sei Yoshida
标识
DOI:10.1101/2022.06.22.497178
摘要
ABSTRACT Circular dorsal ruffles (CDRs) are rounded membrane ruffles induced by growth factors to function as precursors of the large-scale endocytosis called macropinocytosis. In cell line systems, CDR/macropinocytosis regulate the AKT-mTORC1 pathway, a canonical growth factor signaling. However, it is not known if this mechanism occurs in tissues. Here, utilizing ultra-high-resolution scanning electron microscopy, we report that CDRs are expressed in glomerular podocytes ex vivo and in vivo . Biochemical and imaging analysis revealed that AKT phosphorylation is localized to CDRs upstream of mTORC1 activation in podocyte cell line and isolated glomeruli, indicating that CDRs function as signal platforms for AKT-mTORC1 pathway in podocytes to maintain the kidney function. Because mTORC1 has critical roles in the podocyte metabolism and the aberrant activation of mTORC1 triggers podocytopathies, these results suggest that targeting CDR formation would be a potential therapeutic approach for the diseases.
科研通智能强力驱动
Strongly Powered by AbleSci AI