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Fertilization is a complex process that is initiated by
recognition of the zona pellucida of the egg by the spermatozoon.
Sperm bind to the zona pellucida (ZP) and then undergo the acrosome
reaction, an exocytotic event which allows the sperm to digest the ZP
matrix and contact the vitelline membrane of the egg. The acrosome
reaction involves the binding of receptors on the sperm to the zona
pellucida glycoprotein ZP3 (182889),
followed by receptor aggregation and tyrosine phosphorylation of the
receptor. Tyrosine phosphorylation in sperm appears important in this
process, since inhibition of protein tyrosine kinase (PTK) activity
interferes with acrosomal exocytosis and blocks fertilization
(Leyton et al., 1992).
Burks et al. (1995) identified the human
ZP3 receptor in sperm and showed that it has autocatalytic tyrosine
kinase activity. They cloned the cDNA for this protein, which they
termed ZRK (for ZP receptor kinase), by screening a human testis cDNA
library with a monoclonal antibody specific for a 95-kD sperm protein
previously implicated in sperm-ZP interaction (Moore
et al., 1987). The isolated cDNA encodes a protein of 600 amino
acids with a catalytic domain 55% identical to the protein tyrosine
kinase domain of c-Eyk, a receptor-like PTK identified as a
proto-oncogene (Jia and Hanafusa, 1994).
Burks et al. (1995) showed that antibodies
raised against peptides of ZRK recognized a 95-kD human sperm protein
that contains phosphotyrosine and which has kinase activity
stimulated by ZP3. They also showed that synthetic peptides
corresponding to the putative extracellular region of ZRK inhibited
sperm binding to human zona pellucida. Northern blots showed a 2.2-kb
transcript in human testis, but not other tissues.
Mouse sperm recognize and bind a terminal galactose on one class
of O-linked oligosaccharides on ZP3. If the galactose residue is
removed, sperm binding is blocked. Bookbinder
et al. (1995) identified a glycosylated spermatozoon peripheral
membrane protein in mice that binds ZP3. Bookbinder
et al. (1995) purified and partially sequenced this protein,
which they referred to as sp56, and designed degenerate primers for
PCR of mouse testis cDNA. The product was then used as a probe to
screen a cDNA library. The predicted protein contains carbohydrate
binding domains. The sp56 protein is related to the alpha subunit of
complement 4B. It is not related to ZRK. Purified sp56 binds to mouse
eggs and blocks their fertilization. A 2.2-kb sp56 transcript was
detected in mouse testes, but not other tissues. The authors noted
that sperm-egg recognition in mammals is largely species-specific and
serves as a barrier to cross-species fertilization. They detected the
sp56 protein in hamster sperm but not sperm from guinea pigs or
humans using both antibody detection and Northern blotting. They
therefore presumed that a different mechanism is involved in sperm
binding in humans.
Alan F. Scott : 2/8/1996
dkim : 7/30/1998
terry : 5/2/1996
mark : 4/23/1996
mark : 4/23/1996
mark : 2/8/1996