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VE‐cadherin‐mediated signaling regulates microtubule dynamics
Author(s) -
Komarova Yulia,
Garcia Alexander N,
Malik Asrar B.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.357.8
Subject(s) - microbiology and biotechnology , adherens junction , cadherin , ve cadherin , microtubule , phosphorylation , endoplasmic reticulum , chemistry , biology , biochemistry , cell
Disruption of adherens junctions (AJs) in endothelial cells by pro‐inflammatory stimuli such as thrombin induces microtubule (MT) destabilization (Gorovoy et al., J Biol Chem. 2005 280: 26533‐42). Here we determined the signaling mechanism regulating MT dynamics by VE‐cadherin homophilic adhesion. We assessed MT dynamics in human microvascular endothelial monolayers by expressing YFP‐tagged End Binding (EB)‐1 protein, which binds preferentially to the growing ends of MTs. Formation of AJs inhibited MT growth by increasing MT catastrophe frequency whereas disruption of AJs by calcium switch or using VE‐cadherin blocking antibody induced MT persistent growth. We used calcium switch model to address the signaling mechanism downstream of VE‐cadherin adhesion in regulating MT dynamics. We observed that disruption of AJs induced the release of calcium from endoplasmic reticulum and activation of protein phosphatase 2B (PP2B). Using PP2B autoinhibitory peptide we demonstrated that PP2B induced de‐phosphorylation of EB3 (but not EB1 or EB2), the accumulation of EB3 at the MT growing ends, and MT growth. We conclude that signaling activated by VE‐cadherin adhesion regulates MT dynamics through the PP2B‐EB3 axis, and may thereby regulate endothelial cells shape and motility.