CNR - Institute of Neuroscience CNR
Institute of Neuroscience


Stress response proteins in the endoplasmic reticulum: costitutive and inducible expression of GRP94 in skeletal muscle

The glucose-regulated protein Grp94/gp96 is a ER chaperone of the heat shock protein family (Hsp90 homologue), responsive to ER stress.


This chaperone is required for differentiation and maturation of C2C12 muscle cells. Early after induction of muscle differentiation Grp94 is Tyr-phosphorylated. In the ER by an intralumenal Fyn kinasis. This event is required for protein translocation to the Golgi apparatus (Frasson et al.,2009) and finally the cell surface.

In addition,upregulated Grp94 exerts cytoprotection against calcium overload (Vitadello et al.,2003) and oxidative stress (Pizzo et al., 2009), decreased caspase 12 activation, protein oxidation and nuclear translocation of NF-kB, and significantly reduces amount of releasable calcium from intracellular stores.


  • Dalla Libera L, Ravara B, Gobbo V, Tarricone E, Vitadello M, Biolo G, Vescovo G, Gorza L (2009) A transient antioxidant stress response accompanies the onset of disuse atrophy in human skeletal muscle. J. Appl. Physiol. 107:549-57.
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  • Frasson M, Vitadello M, Brunati AM, La Rocca N, Tibaldi E, Pinna LA, Gorza L, Donella-Deana A (2009) Grp94 is Tyr-phosphorylated by Fyn in the lumen of the endoplasmic reticulum and translocates to Golgi in differentiating myoblasts. Biochim. Biophys. Acta 1793:239-52.
  • Tarricone E, Scapin C, Vitadello M, Esposito F, Margonato V, Milano G, Samaja M, Gorza L (2008) Cellular distribution of Hsp70 expression in rat skeletal muscles. Effects of moderate exercise training and chronic hypoxia. Cell Stress Chaperones 13:483-95.
  • Brini M, Miuzzo M, Pierobon N, Negro A, Sorgato MC (2005) The prion protein and its paralogue Doppel affect calcium signaling in Chinese hamster ovary cells. Mol. Biol. Cell 16:2799-808.


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Maurizio Vitadello

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