Santiago Di Pietro

Santiago Di PietroAssociate Professor
Office: MRB 281
Phone: 970-491-5302
Education: Ph.D., University of Buenos Aires
Research Title: Molecular Mechanisms of Intracellular Protein Transport

This laboratory focuses on fundamental aspects of membrane protein transport. We are particularly interested in clathrin mediated endocytosis and transport pathways to lysosomes, melanosomes, platelet dense granules and other lysosome related organelles (LROs). The physiological significance of these pathways is manifold. The endocytic pathway is required for nutrient uptake, down-regulation of signal transduction events, antigen presentation, and virus internalization, while the biosynthetic pathways to lysosomes and LROs are critical for the biogenesis of these organelles. We have gained a solid expertise in the integrated use of biochemistry, biophysics, mammalian and yeast cell biology, and genetics. We are applying that experience to identify new components of the transport machinery protein network, to study novel mechanisms regulating clathrin coat formation, and to understand the link between the transport machinery and the actin cytoskeleton. We expect that our work will have implications not only in basic cell biology but also in deciphering the pathogenesis of diseases associated with defects in protein transport pathways.

Selected Publications

Farrell K.B., McDonald S., Lamb A.K., Worcester C., Peersen O.B., Di Pietro S.M.  Novel function of a dynein light chain in actin assembly during clathrin mediated endocytosis. The Journal of Cell Biology, in press.

Ambrosio A.L., Di Pietro S.M.  Storage pool diseases illuminate platelet dense granule biogenesis. Platelets, 28:138-146, 2017.

Bultema J.J., Di Pietro S.M.  Reduce, reuse, recycle: a retrieval transport pathway for the membrane fusion machinery involved in melanosome biogenesis. Pigment Cell Melanoma Res. 30:10-12, 2017

Ambrosio A.L., Boyle J.A., Aradi A., Christian K.A., Di Pietro S.M.  TPC2 controls pigmentation by regulating melanosome pH and size.  Proc. Natl. Acad. Sci. USA. 113:5622-5627, 2016.

Ambrosio A.L., Boyle J.A., Di Pietro S.M.  TPC2 mediates new mechanisms of platelet dense granule membrane dynamics through regulation of Ca2+ Mol. Biol. Cell. 26:3263-3274, 2015.

Farrell K.B., Grossman C., Di Pietro S.M.  New Regulators of Clathrin-Mediated Endocytosis Identified by Systematic Quantitative Fluorescence Microscopy. Genetics, 201:1061-1070, 2015.

Feliciano D., Tolsma T.O., Farrell K.B., Aradi A., Di Pietro S.M. A second Las17 monomeric actin-binding motif functions in Arp2/3-dependent actin polymerization during endocytosis. Traffic, 16:379-397, 2015.

Bultema J.J., Boyle J.A., Malenke P.B., Martin F.E., Dell'Angelica E.C., Cheney R.E., Di Pietro S.M. Myosin Vc interacts with Rab32 and Rab38 proteins and works in the biogenesis and secretion of melanosomes. J. Biol. Chem. 289: 33513-33528, 2014.

Bultema J.J., Di Pietro S.M. Cell type-specific Rab32 and Rab38 cooperate with the ubiquitous lysosome biogenesis machinery to synthesize specialized lysosome-related organelles. Small GTPases 4: 16-21, 2013.

Ambrosio A.L., Boyle J.A, and Di Pietro S.M. Mechanism of platelet dense granule biogenesis: study of cargo transport and the function of Rab32 and Rab38 in a model system. Blood 120: 4072-4081, 2012.

Feliciano D., and Di Pietro S.M. SLAC, a complex between Sla1 and Las17, regulates actin polymerization during clathrin-mediated endocytosis. Mol. Biol. Cell 23: 4256-4272, 2012.

Bultema J.J., Ambrosio, A.L., Burek, C.L., and Di Pietro S.M. BLOC-2, AP-3, and AP-1 proteins function in concert with Rab38 and Rab32 proteins to mediate protein trafficking to lysosome-related organelles. J. Biol. Chem. 287:19550-19563, 2012.

Feliciano D., Bultema J.J., Ambrosio, A.L., and Di Pietro S.M.  In vivo and in vitro studies of adaptor-clathrin interaction. Journal of Visualized Experiments. 47: doi: 10.3791/2352, 2011.

Di Pietro S.M. *, Cascio D., Feliciano D., Bowie J.U., and Payne G.S. * Regulation of clathrin adaptor function in endocytosis: A novel role for the SAM domain. EMBO J. 29:1033-1044, 2010.* Co-corresponding authors.

Mahadev R.K. *, Di Pietro S.M. *, Olson J.M., Piao H., Payne G.S. § and Overduin M. § (2007) Structure of Sla1p homology domain 1 and interaction with the NPFxD endocytic internalisation motif. EMBO J. 26: 1963-1971. * Co-first authors; § Corresponding authors.

Setty, S.R.G., Tenza, D., Truschel, S.T., Chou, E., Sviderskaya, E.V., Theos, A.C., Lamoreux, M.L., Di Pietro, S.M., Starcevic, M., Bennett, D.C., Dell'Angelica, E.C., Raposo, G., and Marks M.S. (2007) BLOC-1 is required for cargo-specific sorting from vacuolar early endosomes toward lysosome-related organelles. Molecular Biology of the Cell 18: 768-780.

Di Pietro S.M., Falcon-Perez J.M., Tenza D., Setty S.R.G., Marks M.S., Raposo G. and Dell'Angelica E.C. (2006) BLOC-1 interacts with BLOC-2 and the AP-3 complex to facilitate protein trafficking on endosomes. Molecular Biology of the Cell 17: 4027-4038.

Capaldi S., Guariento M., Perduca M., Di Pietro S.M., Santome J.A. and Monaco H.L. (2006) Crystal structure of axolotl (Ambystoma mexicanum) liver bile acid-binding protein bound to cholic and oleic acid. Proteins 64: 79-88.

Di Pietro S.M. and Dell'Angelica E.C. (2005) The Cell Biology of Hermansky-Pudlak Syndrome: Recent Advances. Traffic 6: 525-533.

Gautam R., Chintala S., Li W., Zhang Q., Tan J., Novak E.K., Di Pietro S.M., Dell'Angelica E.C. and Swank R.T. (2004) The Hermansky-Pudlak syndrome 3 (cocoa) protein is a component of the biogenesis of lysosome-related organelles complex-2 (BLOC-2). J. Biol. Chem. 279: 12935-12942.

Di Pietro S.M., Falcon-Perez J.M. and Dell'Angelica E.C. (2004) Characterization of BLOC-2, a Complex Containing the Hermansky-Pudlak Syndrome Proteins HPS3, HPS5 and HPS6. Traffic 5: 276-283.

Di Pietro S.M., Centeno J.M., Cerutti M.L., Lodeiro M.F., Alonso L., Ferreiro D.U., Schwarz F., Goldbaum F. and de Prat Gay G. (2003) Specific antibody-DNA interaction: a novel strategy for tight DNA recognition. Biochemistry 42: 6218-8227.

Di Pietro S.M.*, Corsico, B., Perduca M., Monaco H.L. and Santome J.A. (2003) Structural and biochemical characterization of toad liver fatty acid-binding protein. Biochemistry 42: 8192-8203. *corresponding author

Di Pietro S.M. and Santome J.A. (2002) Structural and biochemical characterization of Calhepatin, an S100-like calcium-binding protein from the liver of lungfish (L. paradoxa). Eur. J. Biochem. 269: 3433-3441.

Di Pietro S.M., Perduca M., Santome J.A., and Monaco H.L. (2001) Crystallization and preliminary X-ray study of two Liver Basic Fatty Acid-Binding Proteins. Acta Crystallogr. D 57: 1903-1905.

Di Pietro S.M. and Santome J.A. (2001) Structural and biochemical characterization of the lungfish (Lepidosiren paradoxa) liver basic fatty acid-binding protein. Arch. Biochem. Biophys. 388: 81-90.

Di Pietro S.M. and Santome J.A. (2000) Isolation, characterization and binding properties of two rat liver fatty acid-binding protein isoforms. Biochem. Biophys. Acta 1478: 186-200.

Di Pietro S.M., Veerkamp J.H. and Santome J.A. (1999) Isolation, amino acid sequence determination and binding properties of two fatty acid-binding proteins from axolotl (Ambystoma mexicanum) liver. Evolutionary implications. Eur. J. Biochem. 259: 127-134.

NIH PubMed Publications List