labslabs.htmlshapeimage_2_link_0
homehome.htmlshapeimage_3_link_0
facilitiesfacilities.htmlshapeimage_4_link_0
seminarsseminars.htmlshapeimage_5_link_0
linkslinks.htmlshapeimage_6_link_0
wassarman
peoplewassarmanlab.htmlshapeimage_8_link_0
publicationswassarmanpub.htmlshapeimage_9_link_0
linkswassarmanlink.htmlshapeimage_10_link_0
http://icahn.mssm.edu/departments-and-institutes/developmental-and-regenerative-biology
 

Wassarman Lab - Research

Overview

    For all animals maintenance of life and speciation depend on the process of fertilization. Fusion of eggs and sperm to form a zygote is the culmination of a complex series of interactions between two highly specialized gametes. In mammals, interactions between gametes begin when free-swimming sperm reach the site of ovulated eggs in the oviduct and then bind to eggs (Fig. 1).


    Our research focuses on mammalian egg and sperm surface components that account for species-restricted binding of sperm to eggs during fertilization. For example, one of these components is a glycoprotein, called ZP3, that is present in the ovulated egg extracellular coat, or zona pellucida (ZP). ZP3 serves as a receptor for sperm during fertilization and as an inducer of the acrosome reaction (Fig. 1). We discovered and characterized ZP3 biochemically and, subsequently, cloned and characterized the gene encoding ZP3. While much of our research has been carried out with mice, ZP3 is present in the ZP of all mammalian eggs, including human eggs, and a ZP3-like glycoprotein is present in the extracellular coat (vitelline envelope) of eggs from amphibians, birds, fish, and many invertebrates.

    Our studies have revealed that ZP3 is synthesized, processed, and secreted by oocytes, the precursors of eggs, during the growth phase of oogenesis (Fig. 2). During growth of the oocyte, ZP3 and two other glycoproteins, called ZP1 and ZP2, assemble into an extensive network of interconnected filaments that constitute the ZP. The filaments consist of ZP2 and ZP3, present every 150 Å, and are interconnected by ZP1. Freeswimming sperm recognize and bind to ZP3 at its sperm combining-site located near the carboxy-terminus of the polypeptide. This region of ZP3 has undergone positive Darwinian selection during evolution, consistent with its proposed role in speciesrestricted binding of sperm to eggs.  Binding to ZP3 activates the signal transduction pathway of sperm that culminates in exocytosis, the acrosome reaction, and enables bound sperm to penetrate the ZP. Therefore, ZP3 is a structural glycoprotein, a speciesrestricted sperm receptor, and an activator of signal transduction (acrosome reaction) when sperm bind to unfertilized eggs.


    All ZP glycoproteins share a large region of polypeptide (approximately 260 amino acids), called the "ZP domain" (Fig. 3). A ZP domain is also present in a wide variety of other proteins of diverse origins and functions. For example, ZP domain containing proteins are components of mammalian and non-mammalian eggs, inner ear, nose, and kidney, as well as the Drosophila cuticle, wing epithelium, and mechanosensory organ. Our research strongly suggests that the ZP domain is a conserved module used for polymerization of extracellular proteins. Since the domain is found in a number of proteins involved in human pathologies, we are also investigating relationships between mutations in the ZP domain and disease.


    In our research, we use a wide variety of contemporary methodology, including transfection of mammalian cells, exon swapping, site-directed mutagenesis, transgenesis, and targeted gene disruption. Overall, the object of our research is to understand the molecular basis of the multiple functions of ZP glycoproteins during mammalian oogenesis, fertilization, and preimplantation development and to understand the role of the ZP domain in normal and diseased states.

 
lab info



Paul M. Wassarman
PROFESSOR
paul.wassarman@mssm.edu

212-241-8616 (office)
212-241-8620 (lab)
212-860-9279 (fax)

lab members:
Litscher, Eveline S.

see photos and more here.

mailto:paul.wassarman@mssm.edu?subject=wassarmanlab.htmlwassarmanlab.htmlshapeimage_15_link_0shapeimage_15_link_1shapeimage_15_link_2
key publications

2013
Wassarman, PM, Litscher, ES,
Biogenesis of the mouse egg's extracellular coat, the zona pellucida.
Current Topics Dev. Biol., 102, 243-266.

2012
Wassarman, PM, Litscher, ES,
Influence of the zona pellucida of the mouse egg on folliculogenesis and fertility.
Intl. J. Dev. Biol., 56, 833-839.

2011
Wassarman PM,
The human sperm’s sweet tooth.
Science, 233, 1708-1709.

2010
Wassarman PM, Litscher ES,
Egg’s ZP3 structure speaks volumes.
Cell, 143, 337-338.

2009
Wassarman PM,
Mammalian fertilization:  The strange case of sperm protein 56.
BioEssays, 31, 153-158.

2008
Wassarman PM,
Zona pellucida glycoproteins.
J. Biol. Chem., 283, 24285-24289.

Wassarman PM,
Fertilization:  Welcome to the fold.
Nature, 456, 586-587.

2002
Wassarman PM,
Channels of communication in the ovary.
Nature Cell Biology, 4, S7-S9.

2001
Wassarman PM, Jovine L, Litscher ES,
A profile of fertilization in mammals.
Nature Cell Biology, 3, E59-E64.

1999
Wassarman PM,
Mammalian fertilization:  Molecular aspects of gamete adhesion, exocytosis, and fusion.
Cell, 96, 175-183.

see more publications here.wassarmanpub.htmlshapeimage_17_link_0
3labs.html