Karen M. Ridge1,2,9, John E. Eriksson3,4,5,9, Milos Pekny6,7,8,9 and Robert D. Goldman1,2,9 1Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois 60611, USA; 2Department of Cell and Developmental Biology, Northwestern University, Chicago, Illinois 60611, USA; 3Cell Biology, Faculty of Science and Technology, Åbo Akademi University, FIN-20521 Turku, Finland; 4Turku Bioscience Centre, University of Turku and Åbo Akademi University, FIN-20521 Turku, Finland; 5Euro-Bioimaging European Research Infrastructure Consortium (ERIC), FIN-20521 Turku, Finland; 6Laboratory of Astrocyte Biology and CNS Regeneration, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, 413 90 Gothenburg, Sweden; 7Florey Institute of Neuroscience and Mental Health, Parkville, Victoria 3052, Australia; 8University of Newcastle, Newcastle, New South Wales 2300, Australia Corresponding author: r-goldmannorthwestern.edu

↵9 These authors contributed equally to this work.

Abstract

More than 27 yr ago, the vimentin knockout (Vim−/−) mouse was reported to develop and reproduce without an obvious phenotype, implying that this major cytoskeletal protein was nonessential. Subsequently, comprehensive and careful analyses have revealed numerous phenotypes in Vim−/− mice and their organs, tissues, and cells, frequently reflecting altered responses in the recovery of tissues following various insults or injuries. These findings have been supported by cell-based experiments demonstrating that vimentin intermediate filaments (IFs) play a critical role in regulating cell mechanics and are required to coordinate mechanosensing, transduction, signaling pathways, motility, and inflammatory responses. This review highlights the essential functions of vimentin IFs revealed from studies of Vim−/− mice and cells derived from them.