Agonist-induced Ca2+ entry determined by inositol 1,4,5-trisphosphate recognition

Damian B. Van Rossum, Randen L. Patterson, Kirill Kiselyov, Darren Boehning, Roxanne K. Barrow, Donald L. Gill, Solomon H. Snyder

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

It has been considered that Ca2+ release is the causal trigger for Ca2+ entry after receptor activation. In DT40 B cells devoid of inositol 1,4,5-trisphosphate receptors (IP3R), the lack of Ca 2+ entry in response to receptor activation is attributed to the absence of Ca2+ release. We reveal in this article that IP 3R recognition of IP3 determines agonist-induced Ca 2+ entry (ACE), independent of its Ca2+ release activity. In DT40 IP3R-/- cells, endogenous ACE can be rescued with type 1 IP3R mutants (both a ΔC-terminal truncation mutant and a D2550A pore mutant), which are defective in Ca2+ release channel activity. Thus, in response to B cell receptor activation, ACE is restored in an IP3R-dependent manner without Ca2+ store release. Conversely, ACE cannot be rescued with mutant IP3Rs lacking IP 3 binding (both the Δ90-110 and R265Q IP3-binding site mutants). We conclude that an IP3-dependent conformational change in the IP3R, not endoplasmic reticulum Ca2+ pool release, triggers ACE.

Original languageEnglish (US)
Pages (from-to)2323-2327
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number8
DOIs
StatePublished - Feb 22 2004

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Inositol 1,4,5-Trisphosphate
B-Lymphocytes
Inositol 1,4,5-Trisphosphate Receptors
Endoplasmic Reticulum
Binding Sites

All Science Journal Classification (ASJC) codes

  • General

Cite this

Van Rossum, Damian B. ; Patterson, Randen L. ; Kiselyov, Kirill ; Boehning, Darren ; Barrow, Roxanne K. ; Gill, Donald L. ; Snyder, Solomon H. / Agonist-induced Ca2+ entry determined by inositol 1,4,5-trisphosphate recognition. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 8. pp. 2323-2327.
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Agonist-induced Ca2+ entry determined by inositol 1,4,5-trisphosphate recognition. / Van Rossum, Damian B.; Patterson, Randen L.; Kiselyov, Kirill; Boehning, Darren; Barrow, Roxanne K.; Gill, Donald L.; Snyder, Solomon H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 8, 22.02.2004, p. 2323-2327.

Research output: Contribution to journalArticle

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AU - Van Rossum, Damian B.

AU - Patterson, Randen L.

AU - Kiselyov, Kirill

AU - Boehning, Darren

AU - Barrow, Roxanne K.

AU - Gill, Donald L.

AU - Snyder, Solomon H.

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