Activation of the endothelial store-operated ISOC Ca 2+ channel requires interaction of protein 4.1 with TRPC4

Donna L. Cioffi, Songwei Wu, Mikhail Alexeyev, Steven Goodman, Michael X. Zhu, Troy Stevens

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Store-operated calcium (SOC) entry represents the principal Ca2+ entry pathway into nonexcitable cells. Despite intensive investigation, mechanisms underlying activation of SOC entry have remained elusive. The endothelial ISOC channel is a Ca2+-selective SOC entry channel to which the transient receptor potential (TRP) proteins TRPC1 and TRPC4 contribute subunits. Activation of ISOC is specifically regulated by the spectrin-actin membrane skeleton; however, the nature of coupling between the ISOC channel and membrane skeleton is unknown. Here we demonstrate that protein 4.1 is an essential component of the ISOC channel gating mechanism. Protein 4.1 interacts with TRPC4 and the membrane skeleton. Deletion of the protein 4.1 binding domain on TRPC4 or peptide competition to the protein 4.1 binding domain prevents ISOC activation. These findings reveal that interaction of protein 4.1 with TRPC4 is required for activation of the endothelial ISOC channel.

Original languageEnglish (US)
Pages (from-to)1164-1172
Number of pages9
JournalCirculation research
Volume97
Issue number11
DOIs
StatePublished - Nov 1 2005
Externally publishedYes

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Skeleton
Protein Binding
Proteins
Calcium
Spectrin
Membranes
Calcium Channels
Ion Channels
Actins
Peptides

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Activation of the endothelial store-operated ISOC Ca 2+ channel requires interaction of protein 4.1 with TRPC4. / Cioffi, Donna L.; Wu, Songwei; Alexeyev, Mikhail; Goodman, Steven; Zhu, Michael X.; Stevens, Troy.

In: Circulation research, Vol. 97, No. 11, 01.11.2005, p. 1164-1172.

Research output: Contribution to journalArticle

Cioffi, Donna L. ; Wu, Songwei ; Alexeyev, Mikhail ; Goodman, Steven ; Zhu, Michael X. ; Stevens, Troy. / Activation of the endothelial store-operated ISOC Ca 2+ channel requires interaction of protein 4.1 with TRPC4. In: Circulation research. 2005 ; Vol. 97, No. 11. pp. 1164-1172.
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