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The Par-Tiam1 complex controls persistent migration by stabilizing microtubule-dependent front-rear polarity
D Michiel Pegtel1, Saskia I J Ellenbroek, Alexander E E Mertens
1The Netherlands Cancer Institute, Division of Cell Biology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Current Biology : CB
|September 11, 2007
Summary
The Par-Tiam1 complex is essential for front-rear cell polarity and persistent migration in keratinocytes. This complex also regulates apical-basal polarity in epithelial cells, demonstrating its versatile role in cell organization.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- Cell polarity is vital for biological functions, regulated by protein complexes like Par3, Par6, and PKCzeta.
- The Par complex and Tiam1 control apical-basal polarity in epithelial cells.
- This study investigates the role of the Par complex and Tiam1 in front-rear polarity during keratinocyte migration.
Purpose of the Study:
- To test if the Par complex and Tiam1 control front-rear polarity in migrating keratinocytes.
- To understand the mechanism by which these proteins influence cell migration and polarity.
- To explore the context-dependent functions of the Par polarity complex.
Main Methods:
- Studied wild-type (WT), Tiam1-deficient (Tiam1 KO), and Par3-depleted keratinocytes.
- Utilized immunoprecipitation to assess protein associations.
- Observed cell polarization, migration patterns, and microtubule stability.
Main Results:
- Tiam1 KO and Par3-depleted keratinocytes exhibit random migration due to unstable front-rear polarity.
- Tiam1 associates with Par3 and PKCzeta in migrating keratinocytes, with enrichment at leading edges.
- Impaired Par-Tiam1 function leads to unstable microtubules, affecting directional migration.
Conclusions:
- The Par-Tiam1 complex stabilizes front-rear polarity, promoting persistent and chemotactic migration in noncontacting cells.
- In contacting epithelial cells, the Par-Tiam1 complex establishes apical-basal polarity.
- The Par polarity complex exhibits functional flexibility, controlling distinct polarities based on cellular context.
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