Requirement of Phospholipase Cδ4 for the Zona Pellucida-Induced Acrosome Reaction

Fukami, Kiyoko; Nakao, Kazuki; Inoue, Takafumi; Kataoka, Yuki; Kurokawa, Manabu; Fissore, Rafael A.; Nakamura, Kenji; Katsuki, Motoya; Mikoshiba, Katsuhiko; Yoshida, Nobuaki; Takenawa, Tadaomi

doi:10.1126/science.1059042

Cited by 184 publications

(117 citation statements)

References 19 publications

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“…In support of this notion, a targeted gene disruption study revealed that PLCd4-null male mice were infertile, and in vitro fertilization experiments showed that, despite exhibiting normal morphology and motility, PLCd4 deficient sperm were unable to fertilize efficiently (Fukami et al, 2001). However, additional ICSI studies showed that mutant sperm were as capable of triggering [Ca 2+ ] i oscillations as wild type sperm (Fukami et al, 2001). Furthermore, injection of recombinant PLCd4 protein failed to initiate oscillations in mouse eggs (Fukami et al, 2001, unpublished observations).…”

Section: Plcd4mentioning

confidence: 96%

“…Moreover, PLCs are well known to be involved in cell growth, differentiation, and cytoskeletal organization (Divecha and Irvine, 1995;Rhee, 2001). To date, 12 PLC isozymes (b1-4, c1-2, d1-4, e, f) have been identified, and expression of PLCb1, b3, c1, and c2 has been noted in mouse eggs (Dupont et al, 1996;Mehlmann et al, 1998;Wang et al, 1998), whereas expression of b1-3, c1-2, d2, d4, and f has been detected in sperm Fukami et al, 2001;Wu et al, 2001b;Parrington et al, 2002;Saunders et al, 2002). Importantly, discriminating whether a PLC(s) from eggs or sperm, or a combination of PLCs from both gametes, plays a role in mammalian fertilization has proven an elusive task.…”

Section: Egg-or Sperm-derived Plcs?mentioning

confidence: 99%

“…Subsequent studies demonstrated that PLCd4 and especially its spliced variant, PLCd4-ALTII, are predominantly expressed in the testis (Lee and Rhee, 1996;Nagano et al, 1999;Fukami et al, 2001), raising the possibility that PLCd4 may be involved in some aspect of spermatogenesis or fertilization. In support of this notion, a targeted gene disruption study revealed that PLCd4-null male mice were infertile, and in vitro fertilization experiments showed that, despite exhibiting normal morphology and motility, PLCd4 deficient sperm were unable to fertilize efficiently (Fukami et al, 2001). However, additional ICSI studies showed that mutant sperm were as capable of triggering [Ca 2+ ] i oscillations as wild type sperm (Fukami et al, 2001).…”

Section: Plcd4mentioning

confidence: 99%

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Mammalian Fertilization: From Sperm Factor to Phospholipase Cζ

Kurokawa

Sato

Fissore

2004

Biology of the Cell

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In mammalian eggs, the fertilizing sperm evokes intracellular Ca 2+ ([Ca 2+ ] i ) oscillations that are essential for initiation of egg activation and embryonic development. Although the exact mechanism leading to initiation of [Ca 2+ ] i oscillations still remains unclear, accumulating studies suggest that a presently unknown substance, termed sperm factor (SF), is delivered from the fertilizing sperm into the ooplasm and triggers [Ca 2+ ] i oscillations. Based on findings showing that production of inositol 1,4,5-trisphosphate (IP 3 ) underlies the generation of [Ca 2+ ] i oscillations, it has been suggested that SF functions either as a phospholipase C (PLC), an enzyme that catalyzes the generation of IP 3 , or as an activator of a PLC(s) pre-existing in the egg. This review discusses the role of SF as the molecule responsible for the production of IP 3 and the initiator of [Ca 2+ ] i oscillations in mammalian fertilization, with particular emphasis on the possible involvement of egg-and sperm-derived PLCs, including PLCf, a novel sperm specific PLC.

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Section: Plcd4mentioning

confidence: 96%

Section: Egg-or Sperm-derived Plcs?mentioning

confidence: 99%

Section: Plcd4mentioning

confidence: 99%

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Mammalian Fertilization: From Sperm Factor to Phospholipase Cζ

Kurokawa

Sato

Fissore

2004

Biology of the Cell

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“…Consistent with this idea, T. cruzi contains a PLC-␦ isoform (41) and PLC-␦ candidate sequences are present in the Plasmodium falciparum and Plasmodium vivax genomes (42). While not conventionally associated with Ca 2ϩ signaling, PLC-␦ has recently been linked to Ca 2ϩ transients associated with fertilization in mice (43). Thus, it is possible that PLC-␦ plays an important role in protozoan calcium regulation.…”

Section: Fig 3 Ethanol Increases T Gondii Ipmentioning

confidence: 99%

Toxoplasma gondii Microneme Secretion Involves Intracellular Ca2+ Release from Inositol 1,4,5-Triphosphate (IP3)/Ryanodine-sensitive Stores

Lovett¹,

Marchesini²,

Moreno³

et al. 2002

Journal of Biological Chemistry

161

162

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Calcium-mediated microneme secretion in Toxoplasma gondii is stimulated by contact with host cells, resulting in the discharge of adhesins that mediate attachment. The intracellular source of calcium and the signaling pathway(s) triggering release have not been characterized, prompting our search for mediators of calcium signaling and microneme secretion in T. gondii. We identified two stimuli of microneme secretion, ryanodine and caffeine, which enhanced release of calcium from parasite intracellular stores. Ethanol, a previously characterized trigger of microneme secretion, stimulated an increase in parasite inositol 1,4,5-triphosphate, implying that this second messenger may mediate intracellular calcium release. Consistent with this observation, xestospongin C, an inositol 1,4,5-triphosphate receptor antagonist, inhibited microneme secretion and blocked parasite attachment and invasion of host cells. Collectively, these results suggest that T. gondii possess an intracellular calcium release channel with properties of the inositol 1,4,5-triphosphate/ryanodine receptor superfamily. Intracellular calcium channels, previously studied almost exclusively in multicellular animals, appear to also be critical to the control of parasite calcium during the initial steps of host cell entry.

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“…1 There are several isoforms of PLC in the spermatozoa (10,11). PLC␦4, in particular, has been implicated in the early events of the acrosome reaction (12). Active PLC would produce inositol 1,4,5-trisphosphate (IP 3 ) that would open IP 3 -sensitive calcium channels in the membrane of intracellular stores.…”

mentioning

confidence: 99%

The Intraacrosomal Calcium Pool Plays a Direct Role in Acrosomal Exocytosis

Blas¹,

Michaut²,

Treviño³

et al. 2002

Journal of Biological Chemistry

119

125

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The acrosome reaction is a unique type of regulated exocytosis. The single secretory granule of the sperm fuses at multiple points with the overlying plasma membrane. In the past few years we have characterized several aspects of this process using streptolysin O-permeabilized human spermatozoa. Here we show that Rab3A triggers acrosomal exocytosis in the virtual absence of calcium in the cytosolic compartment. Interestingly, exocytosis is blocked when calcium is depleted from intracellular stores. By using a membrane-permeant fluorescent calcium probe, we observed that the acrosome actually behaves as a calcium store. Depleting calcium from this compartment by using a light-sensitive chelator prevents secretion promoted by Rab3A. UV inactivation of the chelator restores exocytosis. Rab3A-triggered exocytosis is blocked by calcium pump and inositol 1,4,5-trisphosphate (IP 3 )-sensitive calcium channel inhibitors. Calcium measurements inside and outside the acrosome showed that Rab3A promotes a calcium efflux from the granule. Interestingly, release of calcium through IP 3 -sensitive calcium channels was necessary even when exocytosis was initiated by increasing free calcium in the extraacrosomal compartment in both permeabilized and intact spermatozoa. Our results show that a calcium efflux from the acrosome through IP 3 -sensitive channels is necessary downstream Rab3A activation during the membrane fusion process leading to acrosomal exocytosis.The acrosome reaction is an exocytotic process induced physiologically by the activation of sperm receptors by ligands in the zona pellucida of the oocyte. This interaction initiates a complex transduction mechanism leading to multiple fusions between the outer acrosomal membrane and the overlying plasmalemma resulting in the release of the acrosomal content and exposure of the molecules present on the inner acrosomal membrane.As in other regulated secretory events, calcium plays a central role in acrosome reaction (1). Recent results from different laboratories suggest that a first transient cytosolic calcium increase (probably mediated by T-type calcium channels (2)) leads to a second sustained increase of cytosolic calcium that is necessary for the acrosome reaction (3-9). Although the connection between the two events is not completely clear, the current hypothesis is that the first calcium increase causes the activation of a phospholipase C (PLC).1 There are several isoforms of PLC in the spermatozoa (10, 11). PLC␦4, in particular, has been implicated in the early events of the acrosome reaction (12). Active PLC would produce inositol 1,4,5-trisphosphate (IP 3 ) that would open IP 3 -sensitive calcium channels in the membrane of intracellular stores. The emptying of these stores would trigger the opening of store-operated calcium (SOC) channels in the plasma membrane causing a second and sustained calcium increase that would trigger acrosomal exocytosis (1, 7). Although direct proof for the nature of the calcium stores involved in this mechanism is lacking, severa...

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Requirement of Phospholipase Cδ4 for the Zona Pellucida-Induced Acrosome Reaction

Cited by 184 publications

References 19 publications

Mammalian Fertilization: From Sperm Factor to Phospholipase Cζ

Mammalian Fertilization: From Sperm Factor to Phospholipase Cζ

Toxoplasma gondii Microneme Secretion Involves Intracellular Ca2+ Release from Inositol 1,4,5-Triphosphate (IP3)/Ryanodine-sensitive Stores

The Intraacrosomal Calcium Pool Plays a Direct Role in Acrosomal Exocytosis

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