En nuestro laboratorio estamos interesados en estudiar los procesos celulares que controlan la síntesis, distribución intracelular y degradación de glicolípidos, moléculas anfipáticas sintetizadas en el complejo de Golgi mediante la acción coordinada de glicosíltransferasas y localizados principalmente en membrana plasmática. Los objetivos principales incluyen el estudio de la síntesis y vías de transporte exocítico y endocítico de glicolípidos en células de origen epitelial polarizadas y no polarizadas. Además, se estudia la unión y destino intracelular de anticuerpos anti-glicolípidos provenientes de hibridomas (anticuerpos monoclonales) o de modelos animales de neuropatías periféricas, las cuales transcurren con elevados niveles de anticuerpos (policlonales) anti-glicolípidos. Conocer en detalle estos procesos seguramente ayudara a dilucidar el efecto potencial de anticuerpos anti-glicolípidos asociados a determinadas neuropatías. Otra línea de investigación del laboratorio esta orientada al estudio de los mecanismos que regulan el proceso de acilación de proteínas y las consecuencias de dicha modificación covalente sobre la distribución subcelular de las mismas. Los objetivos principales de esta área de investigación incluyen el estudio de los procesos de palmitoilación-depalmitoilación de las proteínas modelo Ras y GAP-43, así como su consecuencia sobre la asociación a membranas y transporte intracelular de estas proteínas. Además, se investiga el rol funcional de las proteínas Ras y GAP-43 en compartimientos de la vía endocítica, con particular énfasis en endosomas de reciclado.

Microb. Vanina Torres
Becario de CONICET Categoria: Iniciacion Tipo II
vtorres@fcq.unc.edu.ar

Lic. en Qca. María del Pilar Pedro
Becario de CONICET Categoria: Iniciacion Tipo I
ppedro@fcq.unc.edu.ar

Bioquímico Fernando Ruggiero
Becario Foncyt
fruggiero@fcq.unc.edu.ar

Est. Macarena Rodriguez Walker, Ayudante Alumno, Beca de Estímulo a las Vocaciones Científicas (Consejo Interuniversitario Nacional).

• Anti-GM1 IgG antibodies in Guillain-Barre syndrome: fine specificity is associated with disease severity.
  Lardone R.D., Yuki N., Odaka M., Daniotti J.L., Irazoqui F.J. and Nores G.A. Journal of Neurology, Neurosurgery & Psychiatry 81:629-633 (2010).
• Metabolic pathways and intracellular trafficking of gangliosides
  Daniotti J.L. and Iglesias-Bartolomé R. IUBMB Life 63:513-20 (2011).
• Trans-activity of plasma membrane-associated ganglioside sialyltransferase in mammalian cells
  Vilcaes A.A., Torres Demechiles V. and Danioti J.L. Journal of Biological Chemistry 286:31437-31446 (2011).
• GD1a modulates GM-CSF-induced cell proliferation
  Santos A.X., Maia J.E., Crespo P.M., Pettenuzzo L.F., Daniotti J.L., Barbé-Tuana F.M., Martins L.M., Trindade V.M., Borojevic R., Guma F.C. Cytokine 56:600-607 (2011).
• Neobiosynthesis of glycosphingolipids by plasma membrane-associated glycosyltransferases
  Crespo, P.M., Torres Demichelis, V. and Daniotti, J.L.
  Journal of Biological Chemistry 285:29179-29190 (2010)
• Acyl-protein thioesterase 2 catalizes the deacylation of peripheral membrane-associated GAP-43
  Tomatis V.M., Trenchi A., Gomez G.A. and Daniotti J.L.
  PLoS ONE 5(11):e15045 (2010)
• Differential endocytic trafficking of neuropathy-associated antibodies to GM1 ganglioside and cholera toxin in epithelial and neural cells.
  Iglesias-Bartolomé R., Trenchi A., Comín R., Moyano A., Nores G. and Daniotti J.L.
  BBA-Biomembranes (2009)
• Anchored and soluble gangliosides contribute to myelosupportivity of stromal cells.
  Ziulkoski A.L., dos Santosa, A.X.S., Andrade C.M.B., Trindade, V.M.T., Daniotti, J.L., Borojevic, R and Guma, F.C.R.
  Biochemical and Biophysical Research Communications 388:17-20(2009).
• Dual acylation is required for trafficking of growth-associated protein-43 to endosomal recycling compartment via an Arf6-associated endocytic vesicular pathway
  Trenchi A., Gomez G.A. and Daniotti J.L.
  Biochemical Journal 421:357-369 (2009).
• Complex gangliosides are apically sorted in polarized MDCK cells and internalized by clathrin-independent endocytosis.
  Crespo P.M., von Muhlinen N., Iglesias-Bartolomé R. and Daniotti J.L.
  FEBS Journal 275:6043-56 (2008).
• c-Fos activates glycolipid synthesis by activating the first glycosyltransferase of their synthesis.
  Crespo, P.M., Silvestre, D.C., Maccioni, H.J.F., Daniotti, J.L. and Caputto, B.L.
  Journal of Biological Chemistry 283:31163-71 (2008).
• Cloning and functional characterization of two key enzymes of glycosphingolipid biosynthesis in the amphibian Xenopus laevis.
  Luque, M., Crespo, P.M., Monaco , M., Aybar, M., Daniotti, J.L. and Sanchez, S.S.
  Developmental Dynamics 237:112-23 (2008).
• Electrical properties of plasma membrane modulate subcellular distribution of K-Ras.
  Gomez G. and Daniotti J.L.
  FEBS Journal 274:2210-2228 (2007).
• Modulation of GaIT1 and SiaIT1 sub-Golgi localization by SiaIT2 expression reveals an organellar level of glycolipid synthesis control.
  Uliana A.S., Crespo P.M., Martina J.A., Daniotti J.L. and Maccioni H.J.F.
  Journal of Biological Chemistry 281:32852-32860 (2006).
  
• In vivo modulation of epidermal growth factor receptor phosphorylation in mice expressing different gangliosides.
  *Daniotti J.L., Crespo P. and Yamashita T.
  Journal of Cellular Biochemistry 99(5):1442-1451 (2006). * Corresponding author.
• The antibody to GD3 ganglioside, R24, is rapidly endocytosed and recycled back to the plasma membrane via the endocytic recycling compartment. Inhibitory effect of Brefeldin A and monensin.
  Iglesias-Bartolome R., Crespo P.M., Gomez G.A. and Daniotti J.L.
  FEBS Journal 273:1744-1758 (2006).
• Gangliosides of myelosupportive stroma cells are transferred to myeloid progenitors and are required for their survival and proliferation.
  Ziulkoski A., Andrade C., Crespo P., Sisti E., Trindade V., Daniotti J.L., Guma F. and Borojevic, R.
  Biochemical Journal 394:1-9 (2006).
  
• H-Ras dynamically interacts with recycling endosomes in CHO-K1 cells. Involvement of Rab5 and Rab11 in the trafficking of H-Ras to this pericentriolar endocytic compartment
  Gomez G. and Daniotti J.L.
  Journal of Biological Chemistry 280:34997-35010 (2005).
  
• Ganglioside GD3 traffics from trans-Golgi network to plasma membrane by a Rab11-independent and Brefeldin A-insensitive exocytic pathway
  Crespo P.M., Iglesias-Bartolomé R and Daniotti J.L.
  Journal of Biological Chemistry 279:47610-47618 (2004).
  
• Membrane distribution of epidermal growth factor receptors in cells expressing different gangliosides
  Zurita A.R., Crespo P.M., Koritschoner N.P. and Daniotti J.L.
  European Journal of Biochemistry 271:2428-2437 (2004).
  
• Ganglioside glycosyltransferases and newly synthesized gangliosides are excluded from detergent-insoluble complexes of Golgi membranes
  Crespo P.M., Zurita A.R., Giraudo C., Maccioni H.J.F. and Daniotti J.L.
  Biochemical Journal 377:561-568 (2004).
• Enhanced insulin sensitivity in mice lacking ganglioside GM3.
  Yamashita T., Yamamoto A., Mizukami H., Shoshannah B., Norton A., Kono M., Tsuji S., Daniotti J.L., Werth N., Sandhoff K. and Proia R.L.
  Proc. Natl. Acad. Sci. USA 100:3445-3449 (2003).
  
• Effect of gangliosides on the distribution of a glycosylphosphatidylinositol-anchored protein in plasma membrane from CHO-K1 cells.
  Crespo P. M., Zurita A. R. and Daniotti J.L.
  Journal of Biological Chemistry 277:44731-44739 (2002).
• Physical and functional asociation of glycolipid N-acetyl-galactosaminyl and galactosyl transferases in the Golgi aparaturs.
  Giraudo C.G., Daniotti J.L. and Maccioni H.J.F.
  Proc. Natl. Acad. Sci. USA 98:1625-1630 (2001).
• Modulation of epidermal growth factor receptor phosphorylation by endogenously expressed gangliosides.
  Zurita A. R., Maccioni H.J.F. and Daniotti J.L.
  Biochemical Journal 355:465-472 (2001).
  
• Anti-GM1 IgG antibodies in Guillain-Barre syndrome: fine specificity is associated with disease severity. Lardone R.D., Yuki N., Odaka M., Daniotti J.L., Irazoqui F.J. and Nores G.A. Journal of Neurology, Neurosurgery & Psychiatry 81:629-633 (2010)
• Metabolic pathways and intracellular trafficking of gangliosides
  Daniotti J.L. and Iglesias-Bartolomé R. IUBMB Life 63:513-20 (2011)
• Trans-activity of plasma membrane-associated ganglioside sialyltransferase in mammalian cells
  Vilcaes A.A., Torres Demechiles V. and Danioti J.L. Journal of Biological Chemistry 286:31437-31446 (2011)


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