Pablo E. Visconti

Pablo E. Visconti

Professor

Office phone: 413-545-5565

Fax: 413-545-6326

Email: pvisconti [at] vasci [dot] umass [dot] edu

Office location: 427W ISB

Ph.D.: University of Buenos Aires, 1991
Postdoctoral Training: University of Pennsylvania

Honors:
Rockefeller Foundation Postdoctoral Fellow, 1991-1995
Rayard Storey Award, 1999

Classes:
ANIML SCI 521 - Physiology of Reproduction

Signal Transduction Pathways During Sperm Capacitation

Mammalian sperm are not able to fertilize eggs immediately after ejaculation. They acquire fertilization capacity after residing in the female tract for a finite period of time. The physiological changes occurring in the female reproductive tract that render the sperm able to fertilize constitute the phenomenon of sperm capacitation.

Using the mouse as an experimental paradigm, we have demonstrated that conditions conducive to capacitation of cauda epididymal sperm promote the tyrosine phosphorylation of a subset of proteins of Mr 40,000 - 120,000. The increase in protein tyrosine phosphorylation is dependent on the presence of BSA, Ca2+ and NaHCO3 in the medium, and the concentrations of these compounds needed for protein tyrosine phosphorylation to occur are correlated with those required for capacitation.

Serum albumin, usually bovine serum albumin (BSA), is believed to function during capacitation in vitro as a sink for the removal of cholesterol from the sperm plasma membrane. We have demonstrated that cholesterol removal is also essential in the regulation of intracellular signaling that occurs during sperm capacitation.

The transmembrane movements of HCO3- and/or Ca2+ could be responsible for the regulation of sperm cAMP metabolism, since the mammalian sperm adenylyl cyclase is markedly stimulated by these ions. We have also demonstrated that the increase in protein tyrosine phosphorylation as well as capacitation were regulated by a cAMP-dependent pathway involving protein kinase A (PKA).

Simultaneously with our findings, Zeng et al. (Dev. Biol. 1995; 171:554-563) reported that capacitation is accompanied by hyperpolarization of the sperm plasma membrane. Although the molecular basis of capacitation is not well understood, recent work from many laboratories is beginning to lead to a unified hypothesis of how capacitation is controlled and this is summarized in the following model:

Transmembrane and intracellular signaling pathways hypothesized to play a role in regulating sperm capacitation. This model is based on the work from a number of different laboratories.

capacitation

Legend:
(-) indicates negative regulation;
(+) indicates positive regulation.
BSA: bovine serum albumin
Chol, cholesterol
5’AMP, 5’ adenosine monophosphate; PTK, protein tyrosine kinase
PTyr-Ptase, phosphotyrosine phosphatase
PDE, cyclic nucleotide phosphodiesterase.

Goals

My long term goal is to understand how the sperm acquire fertilizing capacity at the molecular level. In particular, I am focusing in several basic questions that arise from the capacitation model in the figure such as:

  1. Which are the protein substrates for tyrosine phosphorylation and how are they involved in the capacitation process?
  2. Which are the tyrosine kinase/s and/or phosphotyrosine phosphatases responsible for the increase in protein tyrosine phosphorylation observed during capacitation?
  3. fig2How capacitation and the capacitation-associated hyperpolarization are regulated by components of the capacitation medium?
  4. How are changes in cAMP, protein tyrosine phosphorylation and hyperpolarization of the sperm plasma membrane integrated to regulate capacitation?
  5. Where in the sperm do the changes in cAMP, protein tyrosine phosphorylation and hyperpolarization occur during capacitation?
  6. How cholesterol removal affects signaling pathways during sperm capacitation?
Wertheimer E, Krapf D, Vega-Beltran JL, Sánchez-Cárdenas C, Navarrete F, Haddad D, Escoffier J, Salicioni AM, Levin LR, Buck J et al..  2013.  Compartmentalization of Distinct cAMP Signaling Pathways in Mammalian Sperm.. J Biol Chem.
Escoffier J, Krapf D, Navarrete F, Darszon A, Visconti PE.  2012.  Flow cytometry analysis reveals a decrease in intracellular sodium during sperm capacitation.. Journal of cell science.
Chávez JC, Hernández-González EO, Wertheimer E, Visconti PE, Darszon A, Treviño CL.  2012.  Participation of the Cl-/HCO3- Exchangers SLC26A3 and SLC26A6, the Cl- Channel CFTR, and the Regulatory Factor SLC9A3R1 in Mouse Sperm Capacitation.. Biology of reproduction. 86(1):1-14.
Visconti P.  2012.  Sperm Bioenergetics in a Nutshell.. Biology of reproduction.
Fierro DF, Acevedo JJ, Martínez P, Escoffier J, Sepúlveda FV, Balderas E, Orta G, Visconti P, Darszon A.  2012.  Electrophysiological evidence for the presence of cystic fibrosis transmembrane conductance regulator (CFTR) in mouse sperm.. Journal of cellular physiology.
Krapf D, Chun Ruan Y, Wertheimer EV, Battistone MA, Pawlak JB, Sanjay A, Pilder SH, Cuasnicu P, Breton S, Visconti PE.  2012.  cSrc is necessary for epididymal development and is incorporated into sperm during epididymal transit.. Developmental biology. 369(1):43-53.
Salicioni AM, Romano FB, Visconti PE.  2012.  Testis-Specific Kinases in male Fertility and as Targets for Contraception. American Pharmaceutical Review. 15(5)
Porambo JR, Salicioni AM, Visconti PE, Platt MD.  2012.  Sperm phosphoproteomics: historical perspectives and current methodologies.. Expert Rev Proteomics. 9(5):533-48.
O'Brien ED, Krapf D, Cabada MO, Visconti PE, Arranz SE.  2011.  Transmembrane adenylyl cyclase regulates amphibian sperm motility through protein kinase A activation.. Developmental biology. 350(1):80-8.
Visconti PE, Krapf D, de la Vega-Beltrán JL, Acevedo JJ, Darszon A.  2011.  Ion channels, phosphorylation and mammalian sperm capacitation.. Asian journal of andrology. 13(3):395-405.
Li Y, Sosnik J, Brassard L, Reese M, Spiridonov NA, Bates TC, Johnson GR, Anguita J, Visconti PE, Salicioni AM.  2011.  Expression and localization of five members of the testis-specific serine kinase (Tssk) family in mouse and human sperm and testis. Molec Hum Reprod. 17(1):42-56.
Sosnik J, Buffone MG, Visconti PE.  2010.  Analysis of CAPZA3 localization reveals temporally discrete events during the acrosome reaction.. Journal of cellular physiology. 224(3):575-80.
Krapf D, Arcelay E, Wertheimer EV, Sanjay A, Pilder SH, Salicioni AM, Visconti PE.  2010.  Inhibition of Ser/Thr phosphatases induces capacitation-associated signaling in the presence of Src kinase inhibitors.. The Journal of biological chemistry. 285(11):7977-85.
Visconti PE, Florman HM.  2010.  Mechanisms of sperm-egg interactions: between sugars and broken bonds.. Science signaling. 3(142):pe35.
Sosnik J, Miranda PV, Spiridonov NA, Yoon S-Y, Fissore RA, Johnson GR, Visconti PE.  2009.  Tssk6 is required for Izumo relocalization and gamete fusion in the mouse.. Journal of cell science. 122(Pt 15):2741-9.
Visconti PE.  2009.  Understanding the molecular basis of sperm capacitation through kinase design.. Proceedings of the National Academy of Sciences of the United States of America. 106(3):667-8.
Miranda PV, Allaire A, Sosnik J, Visconti PE.  2009.  Localization of low-density detergent-resistant membrane proteins in intact and acrosome-reacted mouse sperm.. Biology of reproduction. 80(5):897-904.
Yoon S-Y, Jellerette T, Salicioni AM, Lee HC, Yoo M-S, Coward K, Parrington J, Grow D, Cibelli JB, Visconti PE et al..  2008.  Human sperm devoid of PLC, zeta 1 fail to induce Ca(2+) release and are unable to initiate the first step of embryo development.. The Journal of clinical investigation. 118(11):3671-81.
Arcelay E, Salicioni AM, Wertheimer E, Visconti PE.  2008.  Identification of proteins undergoing tyrosine phosphorylation during mouse sperm capacitation.. The International journal of developmental biology. 52(5-6):463-72.
Wertheimer EV, Salicioni AM, Liu W, Trevino CL, Chavez J, Hernández-González EO, Darszon A, Visconti PE.  2008.  Chloride Is essential for capacitation and for the capacitation-associated increase in tyrosine phosphorylation.. The Journal of biological chemistry. 283(51):35539-50.
Salicioni AM, Platt MD, Wertheimer EV, Arcelay E, Allaire A, Sosnik J, Visconti PE.  2007.  Signalling pathways involved in sperm capacitation.. Society of Reproduction and Fertility supplement. 65:245-59.
Jha KN, Salicioni AM, Arcelay E, Chertihin O, Kumari S, Herr JC, Visconti PE.  2006.  Evidence for the involvement of proline-directed serine/threonine phosphorylation in sperm capacitation.. Molecular human reproduction. 12(12):781-9.
Hernández-González EO, Sosnik J, Edwards J, Acevedo JJ, Mendoza-Lujambio I, López-González I, Demarco I, Wertheimer E, Darszon A, Visconti PE.  2006.  Sodium and epithelial sodium channels participate in the regulation of the capacitation-associated hyperpolarization in mouse sperm.. The Journal of biological chemistry. 281(9):5623-33.
Name Phone Office
Alvau , Antonio Graduate Student (ABBS) 413-545-4050 465A ISB
Gervasi , Maria Gracia Postdoctoral Research Associate 413-545-4050 465A ISB
Navarrete , Felipe Graduate Student (ABBS) 413-545-4050 465A ISB
Paudel , Bidur Graduate Student (ABBS) 413-545-4050 465A ISB
Former Lab Personnel

Eva Wertheimer

Sosnik Julian

Enid Arcelay

Michael Reese

Leticia Vivani

Dario Krapf

Jessica Escoffier