Dipartimento di Medicina Molecolare- Università di Siena

Research in the lab focuses on two important areas at the interface between molecular cell biology and medicine:

Molecular mechanisms in the organization of specialised domains in the sarcoplasmic reticulum of muscle cells
One of the major traits that distinguish eukaryotic from prokaryotic cells is their ability to segregate cellular functions to specific internal compartments, which are basically represented by intracellular organelles. Each of the many types of organelles (lysosomes, mithochondria, endoplasmic reticulum etc.) is devoted to a particular function or set of functions and is, therefore, functionally and structurally distinct from the others. Among intracellular organelles, the endoplasmic reticulum certainly represents the largest membrane system in eukaryotic cells and is primarily involved in lipid and protein synthesis and in Ca2+ storage. These functions are segregated to specific endoplasmic reticulum domains that are basically represented by the smooth and the rough endoplasmic reticulum, although a number of membrane sub-domains are present. An example of this complex sub-compartimentalization is observed in muscle cells where the smooth endoplasmic reticulum is mostly represented by the sarcoplasmic reticulum, a network of tubules and cisternae mainly devoted to Ca2+ storage. We are interested in molecular identification of the mechanisms directing the organization of sarcoplasmic reticulum domains and the targeting of sarcoplasmic reticulum proteins to specific sub-compartments.

Mechanisms that regulate proliferative and differentiative potentials of human adult stem cells

Generation of tissues and organs during development is carried out by stem cells, which are special cells capable to self-renew as well as to give rise to differentiated cells. Embryonic stem cells, which are capable to generate all three tissue layers, are considered multipotent as they can contribute to the entire organism when injected into blastocysts. Stem cells with more restricted potential are present during adult life. These adult stem cells are responsible for the repair and regeneration of specific organs such as the skin, blood, and other organs. Isolation of adult stem cells is difficult because of the poor definition of the phenotype of these cells. Similarly, conditions for expansion of adult stem cells in vitro are also poorly defined. An improvement of our knowledge on the identification and expansion of adult stem cells is of fundamental interest to discover the basic molecular and cellular mechanisms that regulate proliferation and differentiation in these cells. This information is also extremely important if we want to develop new strategies for therapeutic use of these cells in human diseases.

References

1. GIANNINI G., CLEMENTI E., CECI R., MARZIALI G. and SORRENTINO V. Expression of a ryanodine receptor-Ca2+ channel that is regulated by TGFß. 1992. Science 257, 91-94.

2. SORRENTINO V. and VOLPE P. Ryanodine receptors: how many, where and why? 1993. Trends in Pharmacol. Sciences.14, 98-103.

3. GIANNINI G., CONTI A., MAMMARELLA S., SCROBOGNA M. and SORRENTINO V. The ryanodine receptor/Calcium channel genes are widely and differentially expressed in murine brain and peripheral tissues. 1995. Journal of Cell Biology 128, 893-904.

4. BERTOCCHINI F., OVITT C., CONTI A., BARONE V., SCHOLER H.R., BOTTINELLI R., REGGIANI C. and SORRENTINO V. Requirement for the ryanodine receptor type 3 for efficient contraction in neonatal skeletal muscles. 1997. The EMBO Journal. 16, 6956-6963.

5. SONNLEITNER A., CONTI A., BERTOCCHINI F., SCHINDLER H. and SORRENTINO V. Functional properties of the ryanodine receptor type 3 (RyR3) Ca2+ release channel. 1998. The EMBO Journal. 17, 2790-2798.

6. FLUCHER B.E., CONTI A., TAKESHIMA H. and SORRENTINO V. Type 3 and Type 1 ryanodine receptors are colocalized in triads of the same mammalian skeletal muscle fibers. 1999. Journal Cell. Biology 146, 621-30.

7. BALSCHUN D., WOLFER D.P., BERTOCCHINI F., BARONE V., CONTI A., ZUSCHRATTER W., MISSIAEN L., LIPP H.P., FREY U. and SORRENTINO V. Deletion of the ryanodine receptor Type 3 (RyR3) impairs forms of synaptic plasticity and spatial learning. 1999. EMBO Journal 18, 5264-5273.

8. SORRENTINO V., BARONE V. and ROSSI D. Intracellular Ca2+ release channels in evolution. 2000. Curr. Opin. Genetics & Development 10, 662-667.

9. SORRENTINO V. and R. RIZZUTO. Molecular genetics of Ca2+ stores and intracellular Ca2+ signalling. 2001. Trends in Pharmacol. Sciences. 22, 459-464.

10. ROSSI D., SIMEONI I., MICHELI M., BOOTMAN M., LIPP P., ALLEN P.D. and SORRENTINO V. RyR1 and RyR3 Isoforms provide distintct intracellular Ca2+ signals in HEK 293 cells. 2002. J. Cell Science 115, 2497-2504

11. SALANOVA M., PRIORI G., BARONE V., INTRAVAIA E., FLUCHER B., CIRUELA F., MCILHINNEY R.A.J., PARYS J.B., MIKOSHIBA K. AND SORRENTINO V. Homer proteins and InsP3 receptors co-localize in the longitudinal sarcoplasmic reticulum of skeletal muscle fibers. 2002. Cell Calcium 32, 193-200.

12. BAGNATO P., BARONE V., ROSSI D. AND SORRENTINO V. Binding of an Ankyrin-1 isoform to the C-terminus of Obscurin identifies a molecular link between the sarcoplasmic reticulum and myofibrils in striated muscles. 2003. J. Cell. Biology 160, 245-253.

13. SORRENTINO V. Molecular determinants of the structural and functional organization of the sarcoplasmic reticulum 2004 Biochimica et Biophysica Acta 1742 113-118

14. SORRENTINO V. Stem cells and muscle diseases 2004 J Muscle Res Cell Motil. 25, 225-30.