The Short N-terminal Domains of STIM1 and STIM2 Control the Activation Kinetics of Orai1 Channels

• DOI: 10.1074/jbc.c109.010900
• Publication Date: 2009-06-02T01:44:50Z
• Authors: Yandong Zhou; Salvatore Mancarella; Youjun Wang; Chanyu Yue; Michael Ritchie; Donald L. Gill; Jonathan Soboloff
• Keywords: Orai1

STIM1 and STIM2 are dynamic transmembrane endoplasmic reticulum Ca(2+) sensors, coupling directly to activate plasma membrane Orai entry channels. Despite extensive sequence homology, the STIM proteins functionally distinct. We reveal that short variable N-terminal random coil sequences of confer profoundly different activation properties. Using Orai1-expressing HEK293 cells, chimeric replacement 43-amino-acid N terminus with attenuates Orai1-mediated drastically slows store-induced Orai1 channel activation. Conversely, 55-amino-acid substituted within strikingly enhances both constitutive Hence, termini powerful modifiers, functioning in "brake" otherwise channels afforded by its high sensitivity luminal Ca(2+).