In mammals, sperm lack the capability to bind to an oocyte
for an amount of time (typically a minimum of one hour to four hours) following ejaculation. They must first capacitate, or
undergo a suite of changes that allow them to bind the zona pellucida (ZP) and
fertilize the egg. These changes “have been shown to induce optimal
capacitation as defined by tyrosine phosphorylation, hyperactivation, and,
critically, ZP binding.” This ability is critical for the formation of a zygote and, therefore, all human life.
This study by Redgrove et al. intended to
describe a part of capacitation, viz. the movement of proteins arylsulfatase A
(ARSA), sperm adhesion molecule I (SPAMI), and heat shock 70kDa protein 2 (HSPA2),
that is critical for the binding of the zona pellucida.
ARSA has been shown in the CNS to regulate the deposition of
the myelin sheath, but also “implicated in the dispersion of the cumulus matrix
of cumulus-oocyte complexes, as well as in the mediation of ZP adhesion.”SPAMI
also operates in the same dispersion/mediation performances, and HSPA2 is a
molecular chaperone. The three form a stable complex which reorients during
capacitation via reorganization of the plasma membrane. The study speculates
that the initial orientation is that of exposed SPAMI in order to break apart
the cumulus-oocyte matrix while the post-capacitation orientation is that of exposed
ARSA in order to bind to the ZP.
The reorganization of the lemma is heavily predicated on the
efflux of cholesterol that occurs in response to a bicarbonate ion interaction.
Without cholesterol, the membrane’s stability declines, allowing for the reorientation
of the protein complexes. However, the reorganization of the lemma is not
complete until some of the final stages of capacitation. The influx of
bicarbonate ions also induces the activation of protein kinase A (PKA). PKA was
targeted and inhibited by Redgrove et al.; it has shown involvement in “increasing
the…phosphorylation of a multitude of proteins…before these targets are able to
effect [sic] tyrosine phosphorylation. Importantly, [the] results clearly show
that the inhibition of PTK…abrogates the ability of SPAMI and ARSA to reorient
within the plasma membrane. It is therefore possible that tyrosine
phosphorylation of the component(s) of the complex may be critical in driving
the change in its surface orientation.”
The source mechanism of sperm capacitation seems to be tyrosine phosphorylation; it is the ultimate precursor of the change in surface organization
necessary for the HSPA2/ARSA/SPAMI complex to reorient in a way most conducive
for binding to the zona pellucida. The length of the capacitation process can be
attributed to the messenger phosphorylation pathways that must be followed as
well as the time-consuming adjustment of the entire surface of the spermatozoa.
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