Lis1 dysfunction leads to traction force reduction and cytoskeletal disorganization during cell migration

Guo-Wei Jheng; Sung Sik Hur; Chia-Ming Chang; Chun-Chieh Wu; Jia-Shing Cheng; Hsiao-Hui Lee; Bon-Chu Chung; Yang-Kao Wang; Keng-Hui Lin; Juan C Del Álamo; Shu Chien; Jin-Wu Tsai

doi:10.1016/j.bbrc.2018.02.151

Lis1 dysfunction leads to traction force reduction and cytoskeletal disorganization during cell migration

Biochem Biophys Res Commun. 2018 Mar 11;497(3):869-875. doi: 10.1016/j.bbrc.2018.02.151. Epub 2018 Feb 20.

Authors

Affiliations

¹ Institute of Brain Science, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, ROC.
² Department of Bioengineering and Institute of Engineering in Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
³ Department of Life Sciences and Institute of Genome Sciences, School of Life Sciences, National Yang-Ming University, Taipei 112, Taiwan, ROC.
⁴ Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, ROC.
⁵ Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, ROC.
⁶ Institute of Physics, Academia Sinica, Taipei 11529, Taiwan, ROC.
⁷ Department of Mechanical and Aerospace Engineering, University of California, La Jolla, San Diego, CA 92093, USA.
⁸ Institute of Brain Science, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, ROC; Brain Research Center (BRC) and Biophotonics and Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei 112, Taiwan, ROC. Electronic address: tsaijw@ym.edu.tw.

PMID: 29470990
DOI: 10.1016/j.bbrc.2018.02.151

Abstract

Cell migration is a critical process during development, tissue repair, and cancer metastasis. It requires complex processes of cell adhesion, cytoskeletal dynamics, and force generation. Lis1 plays an important role in the migration of neurons, fibroblasts and other cell types, and is essential for normal development of the cerebral cortex. Mutations in human LIS1 gene cause classical lissencephaly (smooth brain), resulting from defects in neuronal migration. However, how Lis1 may affect force generation in migrating cells is still not fully understood. Using traction force microscopy (TFM) with live cell imaging to measure cellular traction force in migrating NIH3T3 cells, we showed that Lis1 knockdown (KD) by RNA interference (RNAi) caused reductions in cell migration and traction force against the extracellular matrix (ECM). Immunostaining of cytoskeletal components in Lis1 KD cells showed disorganization of microtubules and actin filaments. Interestingly, focal adhesions at the cell periphery were significantly reduced. These results suggest that Lis1 is important for cellular traction force generation through the regulation of cytoskeleton organization and focal adhesion formation in migrating cells.

Keywords: Actin; Focal adhesion; Lis1; Microtubule; Migration; Traction force.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

1-Alkyl-2-acetylglycerophosphocholine Esterase / genetics
1-Alkyl-2-acetylglycerophosphocholine Esterase / metabolism*
Animals
Biomechanical Phenomena
Cell Movement*
Cytoskeleton / metabolism*
Fibroblasts / cytology*
Fibroblasts / metabolism
Focal Adhesions / metabolism
Mice
Microtubule-Associated Proteins / genetics
Microtubule-Associated Proteins / metabolism*
NIH 3T3 Cells
RNA Interference

Substances

Microtubule-Associated Proteins
1-Alkyl-2-acetylglycerophosphocholine Esterase
Pafah1b1 protein, mouse