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VE‐cadherin Signaling Induces EB3 Phosphorylation to Suppress Microtubule Growth and Stabilize Adherens Junctions
Author(s) -
Geyer Melissa,
Huang Fei,
Daneshjou Nazila,
Garcia Alexander,
Kreutz Barry,
Mehta Dolly,
Malik Asrar B.,
Komarova Yulia
Publication year - 2012
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.26.1_supplement.lb677
Subject(s) - adherens junction , microbiology and biotechnology , phosphorylation , dephosphorylation , cadherin , adhesion , chemistry , biology , phosphatase , biochemistry , cell , organic chemistry
End Binding (EB) proteins, microtubule (MT) plus‐end factors, promote MT growth in cells. Here we demonstrate an unexpected role of Vascular Endothelial (VE)‐cadherin homotypic adhesion in suppressing MT growth by phosphorylation of EB3 on serine 162. In endothelial monolayers, MTs displayed short episodes of growth; however, disruption of VE‐cadherin‐mediated adhesion by either extracellular Ca 2+ “switch” or treatment with a specific anti‐adhesion peptide resulted in persistent MT growth. MT growth was secondary to increased cytosolic [Ca 2+ ] and EB3 dephosphorylation resulting from the loss of VE‐cadherinmediated adhesion. Inhibition of calcineurin (CaN), the Ca 2+ ‐dependent phosphatase, prevented EB3 dephosphorylation and MT growth. Expression of a phospho‐defective S162A EB3 mutant promoted MT growth in confluent monolayers and destabilized adherens junctions (AJs). Thus, VE‐cadherin outside‐in signaling regulates cytosolic Ca 2+ homeostasis and EB3 phosphorylation, which in turn stabilizes AJs. These results reveal a novel function of VE‐cadherin homotypic interaction in modulating endothelial AJ barrier function through the tuning of MT dynamics. This work was supported by NIH grants R01 HL103922 and Giles F. Filley Memorial Award to Y. K.; R01 HL 45638 to A.B. M.; T32 HL07829‐17 support to M. G. and T32 HL07829‐18 support to N. D.