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Disruption of the endothelial ISOC causes phenotypic changes in pulmonary artery endothelial cells
Author(s) -
Barry Christina Jean,
Cioffi Donna L.,
Wu Songwei,
Alexeyev Mikhail,
Stevens Troy
Publication year - 2007
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.21.6.a1430-b
Subject(s) - trpc , thapsigargin , trpc1 , transient receptor potential channel , transfection , microbiology and biotechnology , hek 293 cells , biology , intracellular , chemistry , receptor , cell culture , biochemistry , genetics
Endothelial cells express the transient receptor potential canonical (TRPC) homologues 1 and 4 that contribute to the molecular basis of a calcium‐selective SOC entry channel, I SOC . We have previously shown that activation of I SOC, by addition of thapsigargin, results in increased permeability and intercellular gap formation in pulmonary artery endothelial cells (PAECs). Activation of the I SOC channel requires protein 4.1 binding on the carboxy terminus of the TRPC4 subunit. The TRPC4‐protein4.1 interaction is mediated by a proline rich region/protein 4.1 binding (prr/4.1) domain on TRPC4. A competitive peptide with a sequence corresponding to the prr/4.1 domain was generated and transfected into PAECs. In these cells, thapsigargin‐induced I SOC was abolished and intercellular gap formation reduced. These data represent acute changes resulting from I SOC disruption. However, chronic effects of TRPC4‐protein 4.1 disruption are unknown. Therefore, PAECs were infected with a retroviral construct stably expressing the peptide corresponding to the prr/4.1 domain. PAECs expressing the prr/4.1 peptide exhibited decreased cell size, increased resistance, and increased proliferation. Thus, constant disruption of the TRPC4‐protein 4.1 interaction causes phenotypic change in PAECs. Supported by HL60024