期刊
JOURNAL OF CELL BIOLOGY
卷 220, 期 9, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.202012114
关键词
-
类别
资金
- Cancer Research UK [A17196, A31287, A24452, A19257]
The study reveals that CYRI-A is a key regulator of macropinosome formation and integrin internalization, being transiently recruited to nascent macropinosomes and dependent on PI3K and RAC1 activity for its function.
The Scar/WAVE complex drives actin nucleation during cell migration. Interestingly, the same complex is important in forming membrane ruffles during macropinocytosis, a process mediating nutrient uptake and membrane receptor trafficking. Mammalian CYRI-B is a recently described negative regulator of the Scar/WAVE complex by RAC1 sequestration, but its other para Logue, CYRI-A, has not been characterized. Here, we implicate CYRI-A as a key regulator of macropinosome formation and integrin internalization. We find that CYRI-A is transiently recruited to nascent macropinosomes, dependent on PI3K and RAC1 activity. CYRI-A recruitment precedes RAB5A recruitment but follows sharply after RAC1 and actin signaling, consistent with it being a local inhibitor of actin polymerization. Depletion of both CYRI-A and -B results in enhanced surface expression of the alpha 5 beta 1 integrin via reduced internalization. CYRI depletion enhanced migration, invasion, and anchorage-independent growth in 3D. Thus, CYRI-A is a dynamic regulator of macropinocytosis, functioning together with CYRI-B to regulate integrin trafficking.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据