Open AccessLoss of PTEN promotes formation of signaling-capable clathrin-coated pits
Author(s) -
Luciana K. RosselliMurai,
Joel A. Yates,
Sei Yoshida,
Julia T. Bourg,
Kenneth K. Y. Ho,
Megan White,
Julia Prisby,
Xinyu Tan,
Margaret Altemus,
Liwei Bao,
Zhifen Wu,
Sarah L. Veatch,
Joel A. Swanson,
Sofía D. Merajver,
Allen Liu
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.208926
Subject(s) - biology , pten , clathrin , microbiology and biotechnology , signal transduction , receptor , endocytosis , pi3k/akt/mtor pathway , genetics
Defective endocytosis and vesicular trafficking of signaling receptors has recently emerged as a multifaceted hallmark of malignant cells. Clathrin-coated pits (CCPs) display highly heterogeneous dynamics on the plasma membrane where they can take from 20 seconds to over a minute to form cytosolic coated-vesicles. Despite the large number of cargo molecules that traffic through CCPs, it is not well understood whether signaling receptors activated in cancer, such as epidermal growth factor receptor (EGFR), are regulated through a specific subset of CCPs. The signaling lipid phosphatidylinositol (3,4,5)-triphosphate (PI(3,4,5)P3), which is dephosphorylated by phosphatase tensin homolog (PTEN), is a potent tumorigenic signaling lipid. Using total internal reflection fluorescence microscopy and automated tracking and detection of CCPs, we find EGF bound EGFR and PTEN are enriched in a distinct subset of short-lived CCPs that corresponded with clathrin-dependent EGF-induced signaling. We demonstrate that PTEN plays a role in the regulation of CCP dynamics. Furthermore, increased PI(3,4,5)P3 results in higher proportion of short-lived CCPs, an effect that recapitulates PTEN deletion. Altogether, our findings provide evidence for the existence of short-lived ‘signaling-capable’ CCPs.