Principal Investigator

Marcela Alejandra Michaut, PhD

Phone: 54-261-4135000 ext. 2758 (Office)
            54-261-4135000 ext 2759 (Laboratory)
Fax: 54-261-4494117
Email: mmichaut@fcm.uncu.edu.ar, mmichaut@gmail.com

PhD: Universidad Nacional de San Luis (San Luis, Argentina), 2001
Postdoctoral Training: University of Pennsylvania (Philadelphia, PA, USA), 2005
Honors: GRIP Research Award 2007

Position:
- Staff Researcher, Argentine Research Council (Investigador Adjunto, CONICET),  Instituto de Histología y Embriología (IHEM-CONICET), School of Medicine,
National University of Cuyo. 5500. Mendoza. Argentina.
- Professor of Molecular Biology,  Instituto de Ciencias Básicas (ICB), National University of Cuyo. 5500. Mendoza. Argentina.

Description of Research

Cytoskeleton reorganization during oocyte maturation

Oocyte meiotic maturation is a complex process that involves coordinated nuclear and cytoplasmic modifications that prepare the oocyte for fertilization. In mouse, oocyte maturation is defined by the transition between prophase I and metaphase II and is accompanied by nuclear envelope breakdown, rearrangement of the cortical cytoskeleton, and meiotic spindle assembly. Nevertheless, oocyte maturation is still poorly understood. Cytoskeleton reorganization and spindle function are affected when protein kinase C (PKC) is activated during meiotic maturation of mouse oocytes, suggesting that PKC is involved in meiosis. Myristoylated alanine-rich C kinase substrate (MARCKS) is a major cytoskeletal protein substrate of PKC involved in several signal transduction pathways. Although, numerous studies have implicated MARCKS in the stabilization of cytoskeletal structures, its cellular functions are still unclear. The targets for the action of PKC phosphorylation in the oocyte are unknown, and relatively little is known about MARCKS during oocyte maturation and egg activation. We are interested in dilucidating MARCKS function and other possible targets of PKC as well in cytoskeleton reorganization during oocyte maturation.

Molecular mechanism of membrane fusion during cortical granule exocytosis in mammalian eggs

Fertilization is a central issue in reproduction for all species. The haploid gametes fuse to generate a diploid zygote with a genetically unique composition. Both the male and female gametes undergo regulated exocytosis - termed the acrosome reaction and the cortical reaction respectively - at different times during their encounter, and the success of fertilization depends on these exocytoses. In the last ten years, our group has identified several factors involved in acrosomal exocytosis and has characterized several stages in the secretion process. Nevertheless, the molecular mechanism of cortical reaction, in particular the membrane fusion during cortical granule (CG) exocytosis, remains to be investigated. Our interest is to characterize the molecular machinery involved in this particular exocytosis to further understand the signal transduction pathway that blocks polispermy in mammalian egg fertilization.

Laboratory members

1. Dr. María Natalia Zanetti (Postdoctoral fellowship, CONICET)
2. Lic. Oscar D. Bello (Doctoral fellowship, CONICET)
3. Lic. Marcelo J. Rodríguez Peña (Doctoral fellowship, CONICET)
4. Lic. Giovanna L. Gallo,  (Doctoral fellowship, CONICET)
5. Lic. María Matilde de Paola (graduate student)
6. Marianela V. Carabajal (undergraduate student)

"From left to right: Oscar, Natalia, Marcela, Giovanna, Marcelo and Matilde"

Present Support

- Global Health Research Initiative Program for New Foreign Investigators (GRIP, Fogarty International Center - National Institute of Health) 2007-2012. Project: Role of MARCKS during mouse oocyte maturation and egg activation.

- National University of Cuyo, 2009-2011. Project: Mechanism of membrane fusion during cortical granules exocytosis in mouse eggs.

Internal collaborations
Our laboratory works in close collaboration with groups in the IHEM leaded by:
- Dr. Claudia Tomes
- Dr. Luis Mayorga

International collaborations
- Dr. Rafael Fissore: University of Massachusetts (Amherst, MA), USA
- Dr. Mitsunori Fukuda: Tohoku University, Japan.

Publications

- Bátiz LF, De Blas GA, Michaut MA, Ramírez AR, Rodríguez F, Ratto MH, Oliver C, Tomes CN, Rodríguez EM, Mayorga LS. Sperm from hyh mice carrying a point mutation in alphaSNAP have a defect in acrosome reaction. PLoS ONE, 2009; 4(3): e4963.

- Schligmann K, Michaut MA, Mcelwee JL, Wolff CA, Travis AJ, Turner RM. Calmodulin and CaMKII in the sperm principal piece: evidence for a motility-related calcium/calmodulin pathway. Journal of Andrology, 28(5):706-16; Sep-Oct 2007.

- Roggero CM, Tomes CN, De Blas GA, Castillo J, Michaut MA, Fukuda M, Mayorga L.  Protein kinase C-mediated phosphorylation of the two polybasic regions of Synaptotagmin VI. Dev. Biol., 285(2):422-35; Sep 15, 2005.

- Michaut MA, Williams C J, Schultz R. Phosphorylated MARCKS: a novel centrosome component that also defines a peripheral subdomain of the cortical actin cap in mouse eggs. Dev Biol., 280(1):26-37; Abril 1, 2005.

- Tomes CN, De Blas G, Michaut M, Farre E, Cherhitin O, Visconti P, Mayorga L. Alpha-SNAP and NSF are required in a priming step during the human sperm acrosome reaction. Mol Hum Reprod., 11(1):43-51; Enero 2005.

- De Blas G, Michaut M, Trevino CL, Tomes C, Yunes R, Darszon A, Mayorga L.   The intraacrosomal calcium pool plays a direct role in acrosomal exocytosis. Journal of  Biological Chemistry. 277(51): 49326-49331;Diciembre 20, 2002.

- Yunes R, Tomes C, Michaut M, De Blas G, Rodruiguez F, Regazzi R, Mayorga L. Rab3A and calmodulin regulate acrosomal exocytosis by mechanisms that do not require a direct interaction.
FEBS Lett. 525(1-3): 126-130; Aug 14, 2002.

- Tomes C, Michaut Marcela, De Blas G, Visconti P, Matti U, Mayorga L. SNARE complex assembly is required for human sperm acrosome reaction. Developmental  Biology. 243(2): 326-338; Marzo 15, 2002.

- Michaut M, De Blas G, Tomes C, Yunes R, Fukuda M, Mayorga L. Synaptotagmin VI participates in the acrosome reaction of human spermatozoa. Developmental Biology. 235(2): 521-529; Jul 15, 2001.

- Michaut M, Tomes C, De Blas G, Yunes R,  Mayorga Luis. Calcium-triggered acrosomal exocytosis in human spermatozoa requires the coordinated  activation of Rab3A and N-ethylmaleimide-sensitive factor. Proceedings of  National Academy of  Sciences of  U S A. 97(18): 9996-10001; Agosto 29, 2000.

- Yunes R, Michaut M, Tomes C, Mayorga Luis. Rab3A triggers the acrosome reaction in permeabilized human spermatozoa. Biology of  Reproduction.  62(4): 1084-1089; Abril 2000.

- Michaut M, Carrasco M, Gimenez MS. Effects of castration on the content and labelling of lipids in male rat liver. Hormone and Metabolic Research. 24(12): 593-594; Diciembre 1992.

Actualizado Agosto 2010