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Zona occludens proteins modulate podosome formation and function
- Source :
- The FASEB Journal. 25:505-514
- Publication Year :
- 2010
- Publisher :
- Wiley, 2010.
-
Abstract
- Podosomes are highly dynamic structures that are involved in cell adhesion and extracellular matrix remodeling. They present as intracellular columns composed of an actin-rich core region and a surrounding ring-like structure containing focal adhesion proteins, actin binders as well as cell signaling molecules. A key player in podosome biogenesis is the scaffolding protein cortactin, which is thought to control actin assembly at the core region. We show that the zona occludens protein 1 (ZO-1), a pivotal tight junction protein and known binding partner of cortactin, is a component of podosomes. In the smooth muscle cell line A7r5, phorbol ester treatment induced a rapid relocation of ZO-1 from the cell cortex and cytosolic pools toward newly formed podosomes. Podosomal localization was also observed for the known ZO-1-binding proteins l-afadin, α-catenin, and phospho-connexin 43. Truncation studies revealed that the actin-binding domain but not the association with cortactin is necessary for ZO-1 recruitment to podosomes. Moreover, impaired ZO-1 expression leads to significantly reduced podosome formation and concomitant decreased matrix degradation at podosomes. Our findings demonstrate that besides their known function in tight junction assembly and intercellular communication, zona occludens proteins and their binding partners may play a novel role in podosome formation and associated function, thus regulating cell adhesion and matrix remodeling.
- Subjects :
- Podosome
Myocytes, Smooth Muscle
Biochemistry
Focal adhesion
Extracellular matrix
Mice
Cell cortex
Genetics
Animals
Humans
Amino Acid Sequence
Cell adhesion
Molecular Biology
Actin
Binding Sites
biology
Chemistry
Membrane Proteins
3T3 Cells
Fibroblasts
Phosphoproteins
Actins
Rats
Cell biology
Gene Expression Regulation
Membrane protein
Zonula Occludens-1 Protein
biology.protein
RNA Interference
Cortactin
Protein Binding
Biotechnology
Subjects
Details
- ISSN :
- 15306860 and 08926638
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- The FASEB Journal
- Accession number :
- edsair.doi.dedup.....3cced334008dc1391dec0ec9fbf53404