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

Biochemical and Biophysical Research Communications
Guo-Wei JhengJin-Wu Tsai

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.

Citations

Jun 12, 2020·Cytoskeleton·Aditya ChhatreRoop Mallik
Nov 19, 2019·Frontiers in Molecular Neuroscience·Hsin-Yun ChangJin-Wu Tsai
Jul 16, 2020·Cell Death & Disease·Wenwen ChenYuehong Yang
Dec 6, 2018·Frontiers in Molecular Neuroscience·Yi-An ChenJin-Wu Tsai
Sep 13, 2020·Science Advances·Julie StouffletIsabelle Caillé
Feb 27, 2021·Biosensors & Bioelectronics·Xinxin HangLingqian Chang
Jul 16, 2021·Frontiers in Cell and Developmental Biology·Min LiuYuehong Yang

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