STIM2 regulates capacitive Ca2+ entry in neurons and plays a key role in hypoxic neuronal cell death.
نویسندگان
چکیده
Excessive cytosolic calcium ion (Ca(2+)) accumulation during cerebral ischemia triggers neuronal cell death, but the underlying mechanisms are poorly understood. Capacitive Ca(2+) entry (CCE) is a process whereby depletion of intracellular Ca(2+) stores causes the activation of plasma membrane Ca(2+) channels. In nonexcitable cells, CCE is controlled by the endoplasmic reticulum (ER)-resident Ca(2+) sensor STIM1, whereas the closely related protein STIM2 has been proposed to regulate basal cytosolic and ER Ca(2+) concentrations and make only a minor contribution to CCE. Here, we show that STIM2, but not STIM1, is essential for CCE and ischemia-induced cytosolic Ca(2+) accumulation in neurons. Neurons from Stim2(-/-) mice showed significantly increased survival under hypoxic conditions compared to neurons from wild-type controls both in culture and in acute hippocampal slice preparations. In vivo, Stim2(-/-) mice were markedly protected from neurological damage in a model of focal cerebral ischemia. These results implicate CCE in ischemic neuronal cell death and establish STIM2 as a critical mediator of this process.
منابع مشابه
STIM2 Regulates Capacitive Ca Entry in Neurons and Plays a Key Role in Hypoxic Neuronal Cell Death
ttp D ow nladed from Excessive cytosolic calcium ion (Ca) accumulation during cerebral ischemia triggers neuronal cell death, but the underlying mechanisms are poorly understood. Capacitive Ca entry (CCE) is a process whereby depletion of intracellular Ca stores causes the activation of plasma membrane Ca channels. In nonexcitable cells, CCE is controlled by the endoplasmic reticulum (ER)–resid...
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ورودعنوان ژورنال:
- Science signaling
دوره 2 93 شماره
صفحات -
تاریخ انتشار 2009