Role of HSC70 protein in maintenance of endoplasmic reticulum CA2+ homeostasis

Abstract

Intracellular calcium homeostasis is disrupted in many neuronal diseases and traumatic brain injuries resulting in endoplasmic reticulum (ER) stress [1]. ER stress and intracellular calcium homeostasis is a hub of signaling mechanisms that determine whether injured neurons will live or die. With survivable injuries neurons seek to restore normal function by several mechanisms including the upregulation of chaperones [2]. Hsc70 (aka Hsp73 and HSPA8) is one of such proteins, which is found to be highly concentrated in neurons. Unlike other chaperones in the HSP family Hsc70 is constitutively expressed and interacts with both cell cycle and apoptosis regulating proteins [3]. Therefore, we tested the hypothesis that Hsc70 regulates neural stem cell fate in response to changes intracellular calcium homeostasis. Currently little is known about the function of this novel chaperone or about the role of ER calcium homeostasis in neural stem cell fate determination and this work is the first to investigate this topic.