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What is the mechanism of store-operated Ca 2+ entry?

What is the mechanism of store-operated Ca 2+ entry?. Measuring [Ca 2+ ] ER and I CRAC in single cells. Miyawaki et al, 1999. The ER sensor for CRAC channel activation has low Ca 2+ affinity. Possible candidates: Low-affinity, high-capacity (calreticulin, BiP, etc)

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What is the mechanism of store-operated Ca 2+ entry?

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  1. What is the mechanism of store-operated Ca2+ entry?

  2. Measuring [Ca2+]ER and ICRAC in single cells Miyawaki et al, 1999

  3. The ER sensor for CRAC channel activation has low Ca2+ affinity Possible candidates: Low-affinity, high-capacity (calreticulin, BiP, etc) Low-affinity, multi-EF hand (CREC family: reticulocalbin, ERC-55, etc)

  4. References Smani et al, 2004 Yao et al, 1999 But see: Scott et al, 2003 Bakowski et al, 2003 Ma et al, 2000 But see: Sugawara et al, 1997 Prakriya & Lewis, 2001

  5. A recent “diffusible messenger” model for SOC activation Smani et al, 2004

  6. The fingerprint of the CRAC channel is a definitive benchmark for evaluating putative CRAC channel genes

  7. The family of mammalian TRP channels Clapham, 2003 TRPC1: Mori et al, 2002 (DT40 knockout, inconsistent phenotype) TRPC3: Philipp et al, 2003 (CRAC mutants, rescues TCR but not TG response) TRPV6: Yue et al, 2001 (pore properties don’t match completely) Cui et al, 2002 (dom negative suppression of Icrac)

  8. Ca2+ signals in a positively selecting environment 5C.C7 B6 thymocytes in B10.BR slice Time compression: 80x, total time 60 min

  9. Calcium signals during positive selection are oscillatory Positive selection Neglect

  10. A reductionist approach to the functions of Ca2+ dynamics in T cells: The Ca2+ clamp Dolmetsch et al, 1998

  11. Frequency selectivity of transcriptional activation and gene expression Dolmetsch et al, 1998

  12. Ca2+ oscillations boost signaling efficiency [Ca] Dinterval vs. Tomida et al, 2003

  13. Delayed phosphorylation and transport of NFAT underlies the signaling efficiency of Ca2+ pulses Tomida et al, 2003

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