Mechanical Ring Interfaces between Adherens Junction and Contractile Actomyosin to Coordinate Entotic Cell-in-Cell Formation
Manna Wang,
Zubiao Niu,
Hongquan Qin,
Banzhan Ruan,
You Zheng,
Xiangkai Ning,
Songzhi Gu,
Lihua Gao,
Zhaolie Chen,
Xiaoning Wang,
Hongyan Huang,
Li Ma,
Qiang Sun
Affiliations
Manna Wang
Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongda Street, Beijing 100071, China; Institute of Molecular Immunology, Southern Medical University, Guangzhou 510515, China
Zubiao Niu
Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongda Street, Beijing 100071, China
Hongquan Qin
Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongda Street, Beijing 100071, China; Institute of Molecular Immunology, Southern Medical University, Guangzhou 510515, China
Banzhan Ruan
Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongda Street, Beijing 100071, China
You Zheng
Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongda Street, Beijing 100071, China
Xiangkai Ning
Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongda Street, Beijing 100071, China
Songzhi Gu
Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongda Street, Beijing 100071, China
Lihua Gao
Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongda Street, Beijing 100071, China
Zhaolie Chen
Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongda Street, Beijing 100071, China
Xiaoning Wang
National Clinic Center of Geriatric, the Chinese PLA General Hospital, Beijing 100853, China
Hongyan Huang
Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Corresponding author
Li Ma
Institute of Molecular Immunology, Southern Medical University, Guangzhou 510515, China; Corresponding author
Qiang Sun
Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongda Street, Beijing 100071, China; Corresponding author
Summary: Entosis is a cell-in-cell (CIC)-mediated death program. Contractile actomyosin (CA) and the adherens junction (AJ) are two core elements essential for entotic CIC formation, but the molecular structures interfacing them remain poorly understood. Here, we report the characterization of a ring-like structure interfacing between the peripheries of invading and engulfing cells. The ring-like structure is a multi-molecular complex consisting of adhesive and cytoskeletal proteins, in which the mechanical sensor vinculin is highly enriched. The vinculin-enriched structure senses mechanical force imposed on cells, as indicated by fluorescence resonance energy transfer (FRET) analysis, and is thus termed the mechanical ring (MR). The MR actively interacts with CA and the AJ to help establish and maintain polarized actomyosin that drives cell internalization. Vinculin depletion leads to compromised MR formation, CA depolarization, and subsequent CIC failure. In summary, we suggest that the vinculin-enriched MR, in addition to CA and AJ, is another core element essential for entosis.
