Cross-regulations of two connected domains form a mechanical circuit for steady force transmission during clathrin-mediated endocytosis

IF 7.5 1区 生物学 Q1 CELL BIOLOGY
Yuan Ren, Jie Yang, Barbara Fujita, Yongli Zhang, Julien Berro
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Abstract

Mechanical forces are transmitted from the actin cytoskeleton to the membrane during clathrin-mediated endocytosis (CME) in the fission yeast Schizosaccharomyces pombe. End4p directly transmits force in CME by binding to both the membrane (through the AP180 N-terminal homology [ANTH] domain) and F-actin (through the talin-HIP1/R/Sla2p actin-tethering C-terminal homology [THATCH] domain). We show that 7 pN force is required for stable binding between THATCH and F-actin. We also characterized a domain in End4p, Rend (rod domain in End4p), that resembles R12 of talin. Membrane localization of Rend primes the binding of THATCH to F-actin, and force-induced unfolding of Rend at 15 pN terminates the transmission of force. We show that the mechanical properties (mechanical stability, unfolding extension, hysteresis) of Rend and THATCH are tuned to form a circuit for the initiation, transmission, and termination of force between the actin cytoskeleton and membrane. The mechanical circuit by Rend and THATCH may be conserved and coopted evolutionarily in cell adhesion complexes.

Abstract Image

在凝集素介导的内吞过程中,两个相连结构域的交叉调节形成了稳定传力的机械回路
在裂殖酵母 Schizosaccharomyces pombe 的凝集素介导的内吞(CME)过程中,机械力从肌动蛋白细胞骨架传递到膜。End4p 通过与膜(通过 AP180 N 端同源结构域 [ANTH])和 F-肌动蛋白(通过 talin-HIP1/R/Sla2p 肌动蛋白拴系 C 端同源结构域 [THATCH])结合,在 CME 中直接传递力。我们发现,THATCH 与 F-肌动蛋白之间的稳定结合需要 7 pN 的力。我们还鉴定了 End4p 中的一个结构域 Rend(End4p 中的杆状结构域),它与 talin 的 R12 相似。Rend 的膜定位促使 THATCH 与 F-肌动蛋白结合,在 15 pN 的力诱导下,Rend 展开,从而终止了力的传递。我们的研究表明,Rend 和 THATCH 的机械特性(机械稳定性、解折扩展、滞后)经过调整,在肌动蛋白细胞骨架和膜之间形成了一个力的启动、传递和终止回路。Rend和THATCH的机械回路可能在细胞粘附复合体中得到保存和进化。
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来源期刊
Cell reports
Cell reports CELL BIOLOGY-
CiteScore
13.80
自引率
1.10%
发文量
1305
审稿时长
77 days
期刊介绍: Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.
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