Chaperone Proteins In Muscle Differentiation And Disease

see Vitadello et al. 2014a

Description

This program investigates the cytoprotective role of molecular chaperones in skeletal and heart myocytes. In particular, we are interested in the role of the glucose-regulated protein Grp94, the exclusive endoplasmic-reticulum chaperone of IGFs and integrins and a calcium-binding protein. Our investigations with myogenic cell lines demonstrated that the subcellular redistribution of this chaperone from the endoplasmic reticulum to the sarcolemma is required to promote myoblast differentiation and fusion and is regulated by Tyr-phosphorylation (Gorza and Vitadello, 2000 and Frasson et al., 2009). Increased Grp94 protein levels positively influence muscle cell survival against calcium overload, ischemia and oxidative stress by decreasing the amount of releasable calcium from the stores (Vitadello et al., 2001 and 2003, Pizzo et al., 2010) and maintain skeletal myocyte trophism challenged by unloading by hampering nNOS untethering from sarcolemma (Vitadello et al., 2014a and b). Current investigations will focus on the identification of interacting proteins that i) mediate Grp94 effects on calcium homeostasis and cytoprotection and ii) regulate Grp94-nNOS trafficking to sarcolemma.

5 recent publications

  • Pizzo P, Scapin S, Vitadello M, Florean C, Gorza L (2010). Grp94 acts as a mediator of curcumin-induced anti-oxidant defence in myogenic cells. J Cell Mol Med. 14, 970-81
  • Vitadello M, Doria A, Tarricone E, Ghirardello A, Gorza L. (2010). Myofiber stress-response in myositis:  parallel investigations on patients and experimental animal models of muscle regeneration and systemic  inflammation. Arthritis Res Ther 12:R52, doi:10.1186/ar2963.
  • Renaud G, Llano-Diez M, Ravara B, Gorza L, Feng HZ, Jin JP, Cacciani N, Gustafson AM, Ochala J,  Corpeno R, Li M, Hedstrom Y, Ford GC, Nair KS, Larsson L. (2013). Sparing of muscle mass and function  by passive loading in an experimental intensive  care unit model. J Physiol 591, 1385-1402.
  • Vitadello M, Gherardini J, Gorza L (2014a). The Stress Protein/Chaperone Grp94 Counteracts Muscle Disuse Atrophy by Stabilizing Subsarcolemmal nNOS. Antioxid Redox Signal 20:2479-2496.
  • Vitadello M, Germinario E, Ravara B, Dalla Libera L, Danieli Betto D, Gorza L. (2014b). Curcumin counteracts loss of force and atrophy of unloaded hindlimb rat soleus by hampering neuronal nitric oxide synthase untethering from sarcolemma. J Physiol 592:2637–2652

 

Grants

  • Institutional (ex 60%) and departmental grants