Vimentin filament organization and stress sensing depend on its single cysteine residue and zinc binding.

Nat Commun

Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (C.S.I.C.), Ramiro de Maeztu, 9, 28040 Madrid, Spain.

Published: June 2015

The vimentin filament network plays a key role in cell architecture and signalling, as well as in epithelial-mesenchymal transition. Vimentin C328 is targeted by various oxidative modifications, but its role in vimentin organization is not known. Here we show that C328 is essential for vimentin network reorganization in response to oxidants and electrophiles, and is required for optimal vimentin performance in network expansion, lysosomal distribution and aggresome formation. C328 may fulfil these roles through interaction with zinc. In vitro, micromolar zinc protects vimentin from iodoacetamide modification and elicits vimentin polymerization into optically detectable structures; in cells, zinc closely associates with vimentin and its depletion causes reversible filament disassembly. Finally, zinc transport-deficient human fibroblasts show increased vimentin solubility and susceptibility to disruption, which are restored by zinc supplementation. These results unveil a critical role of C328 in vimentin organization and open new perspectives for the regulation of intermediate filaments by zinc.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458873PMC
http://dx.doi.org/10.1038/ncomms8287DOI Listing

Publication Analysis

Top Keywords

vimentin
11
vimentin filament
8
vimentin organization
8
zinc
7
filament organization
4
organization stress
4
stress sensing
4
sensing depend
4
depend single
4
single cysteine
4

Similar Publications

Pancreatic cancer is an aggressive tumor, which is often associated with a poor clinical prognosis and resistance to conventional chemotherapy. Therefore, there is a need to identify new therapeutic markers for pancreatic cancer. Although KIN17 is a highly expressed DNA‑ and RNA‑binding protein in a number of types of human cancer, its role in pancreatic cancer development, especially in relation to progression, is currently unknown.

View Article and Find Full Text PDF

Metastasis is the trigger of death in anaplastic thyroid cancer (ATC) patients, yet the specific mechanisms at play are still largely enigmatic. While the involvement of LARP1 in the metastatic process of various cancers has been documented, there is a noticeable gap in the literature regarding its potential influence on ATC metastasis. Molecular studies probed LARP1 expression within ATC cells, with subsequent in vitro experiments examining the effects of LARP1 on ATC cell metastasis and the mTOR signaling cascade.

View Article and Find Full Text PDF

A male in his seventies presented with lung cancer in the right lower lobe. The surgically resected specimen revealed a pleomorphic carcinoma featuring an adenocarcinoma component with lepidic, acinar, and papillary patterns, alongside a spindle cell component spreading along the pulmonary artery wall, resembling intimal sarcoma. The spindle tumor cells were positive for keratins, TTF-1, napsin A, and vimentin, but negative for p40, CK14, desmin, alpha-smooth muscle actin, CDK4, and MDM2.

View Article and Find Full Text PDF

Objective: Elevated systolic blood pressure and increased pulse pressure are closely associated with renal damage; however, the exact mechanism remains unclear. Therefore, we investigated the effects of increased pulse pressure on tubulointerstitial fibrosis and renal damage in elderly rats with isolated systolic hypertension (ISH). Additionally, the role of renal tubular epithelial-mesenchymal transition (EMT) and its upstream signalling pathways were elucidated.

View Article and Find Full Text PDF

Exploring vimentin's role in breast cancer via PICK1 alternative polyadenylation and the miR-615-3p-PICK1 interaction.

Biofactors

January 2025

Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Tongji University, Shanghai, People's Republic of China.

Breast cancer continues to be a major health issue for women worldwide, with vimentin (VIM) identified as a crucial factor in its progression due to its role in cell migration and the epithelial-to-mesenchymal transition (EMT). This study focuses on elucidating VIM's regulatory mechanisms on the miR-615-3p/PICK1 axis. Utilizing the 4T1 breast cancer cell model, we first used RNA-seq and proteomics to investigate the changes in the APA of PICK1 following VIM knockout (KO).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!