Intermediate filament-associated cytolinker plectin 1c destabilizes microtubules in keratinocytes
Open Access
- 15 March 2013
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 24 (6), 768-784
- https://doi.org/10.1091/mbc.e12-06-0488
Abstract
The transition of microtubules (MTs) from an assembled to a disassembled state plays an essential role in several cellular functions. While MT dynamics are often linked to those of actin filaments, little is known about whether intermediate filaments (IFs) have an influence on MT dynamics. We show here that plectin 1c (P1c), one of the multiple isoforms of the IF-associated cytolinker protein plectin, acts as an MT destabilizer. We found that MTs in P1c-deficient (P1c−/−) keratinocytes are more resistant toward nocodazole-induced disassembly and display increased acetylation. In addition, live imaging of MTs in P1c−/−, as well as in plectin-null, cells revealed decreased MT dynamics. Increased MT stability due to P1c deficiency led to changes in cell shape, increased velocity but loss of directionality of migration, smaller-sized focal adhesions, higher glucose uptake, and mitotic spindle aberrations combined with reduced growth rates of cells. On the basis of ex vivo and in vitro experimental approaches, we suggest a mechanism for MT destabilization in which isoform-specific binding of P1c to MTs antagonizes the MT-stabilizing and assembly-promoting function of MT-associated proteins through an inhibitory function exerted by plectin's SH3 domain. Our results open new perspectives on cytolinker-coordinated IF-MT interaction and its physiological significance.Keywords
This publication has 77 references indexed in Scilit:
- Regulation of cell migration by dynamic microtubulesSeminars in Cell & Developmental Biology, 2011
- The Structure of the Plakin Domain of Plectin Reveals a Non-canonical SH3 Domain Interacting with Its Fourth Spectrin RepeatJournal of Biological Chemistry, 2011
- Targeted Inactivation of a Developmentally Regulated Neural Plectin Isoform (Plectin 1c) in Mice Leads to Reduced Motor Nerve Conduction VelocityJournal of Biological Chemistry, 2009
- Plectin Isoform-dependent Regulation of Keratin-Integrin α6β4 Anchorage via Ca2+/CalmodulinPublished by Elsevier BV ,2009
- Microtubule assembly, organization and dynamics in axons and dendritesNature Reviews Neuroscience, 2009
- ACF7 Regulates Cytoskeletal-Focal Adhesion Dynamics and Migration and Has ATPase ActivityCell, 2008
- A quantitative atlas of mitotic phosphorylationProceedings of the National Academy of Sciences of the United States of America, 2008
- Plectin isoform 1b mediates mitochondrion–intermediate filament network linkage and controls organelle shapeThe Journal of cell biology, 2008
- Myofiber integrity depends on desmin network targeting to Z-disks and costameres via distinct plectin isoformsThe Journal of cell biology, 2008
- Plectin-controlled keratin cytoarchitecture affects MAP kinases involved in cellular stress response and migrationThe Journal of cell biology, 2006