Molecular and Cellular Endocrinology 187 (2002) 139 – 144
Intracellular calcium regulation in sperm capacitation and
acrosomal reaction
Haim Breitbart *
Faculty of Life Sciences, Bar -Ilan Uniersity, Ramat Gan 52900, Israel
Abstract
Binding to the egg’s zona pellucida stimulates the spermatozoon to undergo acrosome reaction, a process which enables the
sperm to penetrate the egg. Prior to this binding, the spermatozoa undergo in the female reproductive tract a series of biochemical
transformations, collectively called capacitation. The first event in capacitation is the elevation of intracellular calcium and
bicarbonate to activate adenylyl cyclase (AC) to produce cyclic-AMP, which activates protein kinase A (PKA) to phosphorylate
certain proteins. During capacitation, there is also an increase in actin polymerization and in the membrane-bound phospholipase
C (PLC). Sperm binding to zona-pellucida causes further activation of cAMP/PKA and protein kinase C (PKC), respectively.
PKC opens a calcium channel in the plasma membrane. PKA together with inositol-trisphosphate activate calcium channels in the
outer acrosomal membrane, which leads to an increase in cytosolic calcium. The depletion of calcium in the acrosome will activate
a store-operated calcium entry mechanism in the plasma membrane, leading to a higher increase in cytosolic calcium, resulting in
membrane fusion and acrosome reaction. © 2002 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Calcium; Regulation; Sperm; Capacitation; Acrosome reaction
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1. Introduction
Mammalian spermatozoa are unable to fertilize the
egg immediately after ejaculation. They require a period
of incubation in the female reproductive tract in order
to acquire the capacity to fertilize. During this time, the
spermatozoa undergo a poorly defined process of matu-
ration known as capacitation. There is no clear recog-
nizable marker for the occurrence of capacitation,
although several intracellular changes are known to
occur including increases in membrane fluidity, choles-
terol efflux, intracellular Ca
2 +
and cAMP concentra-
tions, protein tyrosine phosphorylation, and changes in
swimming patterns and chemotactic motility.
Binding to the zona pellucida stimulates the sperma-
tozoon to undergo the acrosome reaction in which the
outer acrosomal membrane fuses with the overlying
plasma membrane (Yanagimachi, 1995). This exocy-
totic event results in the release of hydrolytic enzymes,
principally, the trypsin like acrosin, and in the exposure
of new membrane domains, both of which are essential
for the fertilization process. In order to penetrate the
zona pellucida the spermatozoon creates a groove
which is approximately the width and height of the
head (Allen and Green, 1997). Here an overview of the
processes involved in intracellular Ca
2 +
regulation re-
sponsible for the acrosome reaction is provided.
2. Protein tyrosine kinase
Tyrosine phosphorylation of proteins plays an im-
portant role in capacitation (Visconti and Kopf, 1998),
acrosome reaction and sperm penetration (Burks et al.,
1995). Inhibitors of protein kinase A (PKA) inhibit
both protein tyrosine phosphorylation and capacitation
of spermatozoa (Visconti et al., 1995). In human sper-
matozoon, reactive oxygen species (ROS) up-regulate
protein tyrosine phosphorylation of several proteins
(Aitken et al., 1995; Leclerc et al., 1997). These obser-
vations are consistent with the suggestion that H
2
O
2
activates adenylyl cyclase to produce cAMP and the
subsequent activation of the serine/threonine kinase A
(Aitken, 1997). It has been suggested that Ca
2 +
and
HCO
3
-
are also required for the activation of sperm
adenylyl cyclase (Visconti et al., 1995).
* Tel.: +972-3-5318201; fax: +972-3-5344766.
E-mail address: breith@mail.biu.ac.il (H. Breitbart).
0303-7207/02/$ - see front matter © 2002 Elsevier Science Ireland Ltd. All rights reserved.
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