TY - JOUR
T1 - Agonist-induced Ca2+ entry determined by inositol 1,4,5-trisphosphate recognition
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.
PY - 2004/2/22
Y1 - 2004/2/22
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.0308565100
DO - 10.1073/pnas.0308565100
M3 - Article
C2 - 14983008
AN - SCOPUS:1442330472
SN - 0027-8424
VL - 101
SP - 2323
EP - 2327
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 8
ER -