LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility.
Hyang Mi Moon1, Simon Hippenmeyer2, Liqun Luo2
1Department of Pediatrics, Institute for Human Genetics, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States.
Elife
|March 12, 2020
Summary
Loss of LIS1 disrupts cell division by affecting microtubule (MT) stability and actomyosin function. This leads to abnormal daughter cell separation in neural progenitor cells (NPCs) and fibroblasts.
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Heterozygous loss of human PAFAH1B1 (LIS1) disrupts neurogenesis and neuronal migration.
- LIS1 regulates microtubule (MT) stability, dynein motor function, and mitotic spindle orientation.
- Recent studies suggest LIS1 controls terminal cell division length in outer radial glial (oRG) progenitors.
Purpose of the Study:
- To investigate the role of LIS1 in late mitotic stages of neural progenitor cells (NPCs) and mouse embryonic fibroblasts (MEFs).
- To examine the cellular mechanisms underlying daughter cell separation defects in Pafah1b1-deficient mutants.
Main Methods:
- In vivo examination of late mitotic stages in Pafah1b1-deficient neocortical NPCs.
- In vitro analysis of Pafah1b1-deficient mouse embryonic fibroblasts (MEFs).
- Assessment of cleavage plane, furrow-associated markers, actomyosin function, and cell membrane contractility.
Main Results:
- Pafah1b1-deficient NPCs and MEFs displayed cleavage plane displacement and mislocalized furrow-associated markers.
- Actomyosin dysfunction and increased cell membrane hyper-contractility were observed in mutants.
- These defects suggest a failure in proper daughter cell separation.
Conclusions:
- LIS1 is crucial for regulating cell membrane contractility during cytokinesis.
- LIS1 acts as a molecular link between MTs/dynein and the actomyosin cytoskeleton.
- Proper daughter cell separation relies on LIS1-mediated control of actomyosin contractility.
Keywords:
LIS1cleavagedevelopmental biologyembryonic fibroblastmitosismouseneocortexneural progenitorMore Related Videos
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