Sorrentino Vincenzo

 

Vie di segnalazione che regolano il metabolismo cellulare

Domini di membrana specializzati nella regolazione della contrazione muscolare

Modelli cellulari e murini di patologie muscolari

 

Human diseases are due to the altered functioning of the cells of our body. Therefore, understanding at the molecular level the organization of the machinery that carry on the many activities of our cells is mandatory for health and for developing novel pharmacological products.

Our research group has acquired over the years a wide range of expertise in molecular, cellular and genetic techniques, including transgenic mouse models and stem cells. This expertise allowed us to identify and characterize several genes and to demonstrate how mutations in these genes result in human genetic diseases.

The main topics of our research activities are skeletal muscle cells and genetic muscular diseases.

The voluntary movements of our body are based on the contractile activity of skeletal muscles (1-3). Skeletal muscle fibers present a high level of organization where the sarcoplasmic reticulum, the mitochondria, the extra-sarcomeric cytoskeleton as well as the costamere at the sarcolemma are perfectly aligned with the myofilaments.

We are interested in understanding the molecular mechanisms that underlay the complex organization of the sarcoplasmic reticulum, how this organelle is interconnected with the contractile apparatus and how the proteins involved in Calcium release from the sarcoplasmic reticulum are assembled at specific sites of the sarcoplasmic reticulum (6,7). Furthermore, we are studying a group of proteins that by connecting the myofibrils with the cytoskeleton contribute to the organization of costameric proteins like dystrophin (6,8).

Mutations in genes responsible of the structural and functional organization of skeletal muscle fibers have been found to cause several genetic diseases. In the recent years, our group has identified and characterized several genes that when mutated are responsible of severe muscle diseases like Malignant Hyperthermia, Central Core Diseases and new forms of muscle myopathy and muscular dystrophy (4,5,8,9).

Interestingly, many genes that regulate the organization and the activity of skeletal muscles are also active in cardiac and smooth muscles. Accordingly, we are extending our research interests into these muscles types.

 

Linee di ricerca specifiche

1) Molecular and cellular biology of muscle cells.

2) The biology of stem cells.

3) Human genetic diseases: diagnosis and mechanisms of disease.

 

Pubblicazioni selezionate

1.     Sorrentino V, Pepperkok R, Davis RL, Ansorge W, Philipson L. Cell proliferation inhibited by MyoD1 independently of myogenic differentiation. Nature. 1990 Jun 28;345 :813-5.

2.     Giannini G, Clementi E, Ceci R, Marziali G, Sorrentino V. Expression of a ryanodine receptor-Ca2+ channel that is regulated by TGF-beta. Science. 1992 Jul 3;257(5066):91-4.  

3.     Bertocchini F, Ovitt CE, Conti A, Barone V, Schöler HR, Bottinelli R, Reggiani C, Sorrentino V. Requirement for the ryanodine receptor type 3 for efficient contraction in neonatal skeletal muscles. EMBO J. 1997 Dec 1;16(23):6956-63.   

4.     Priori SG, Napolitano C, Tiso N, Memmi M, Vignati G, Bloise R, Sorrentino V, Danieli GA. Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia.  Circulation. 2001 Jan 16;103(2):196-200 .

5.     Galli L, Orrico A, Lorenzini S, Censini S, Falciani M, Covacci A, Tegazzin V, Sorrentino V. Frequency and localization of mutations in the 106 exons of the RYR1 gene in 50 individuals with malignant hyperthermia.  Hum Mutat. 2006 Aug;27(8):830. PubMed PMID: 16835904.  

6.     Bagnato P, Barone V, Giacomello E, Rossi D, Sorrentino V. Binding of an ankyrin-1 isoform to obscurin suggests a molecular link between the sarcoplasmic reticulum and myofibrils in striated muscles. J Cell Biol. 2003 Jan 20;160(2):245-53. Epub 2003 Jan 13    

7.     Cusimano V, Pampinella F, Giacomello E, Sorrentino V. Assembly and dynamics of proteins of the longitudinal and junctional sarcoplasmic reticulum in skeletal muscle cells. Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4695-700.

8.     Randazzo D, Giacomello E, Lorenzini S, Rossi D, Pierantozzi E, Blaauw B, Reggiani C, Lange S, Peter AK, Chen J, Sorrentino V. Obscurin is required for ankyrinB-dependent dystrophin localization and sarcolemma integrity. J Cell Biol. 2013 Feb 18;200(4):523-36 .

9.     Orrico A, Lam C, Galli L, Dotti MT, Hayek G, Tong SF, Poon PM, Zappella M, Federico A, Sorrentino V. MECP2 mutation in male patients with non-specific X-linked mental retardation. FEBS Lett. 2000 Sep 22;481(3):285-8.