Cholesterol content regulates acrosomal exocytosis by enhancing Rab3A plasma membrane association

Belmonte, Silvina; Lopez, Cecilia I.; Roggero, Carlos M.; Blas, Gerardo A. De; Tomes, Claudia N.; Mayorga, Luis S.

doi:10.1016/j.ydbio.2005.07.001

Cited by 56 publications

(51 citation statements)

References 62 publications

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“…As reported in Table 1, 70% of oocytes showed the presence of female and male pronuclei following IVF with capacitated mouse sperm, compared to 3% of those fertilized with resting sperm. In addition, reduction in membrane cholesterol content (down to ~45%), an hallmark of capacitation (Go and Wolf, 1985;Belmonte et al, 2005;Gadella et al, 2008), was documented in capacitated versus resting sperm (Table 2), further corroborating that the capacitation process was fully effective.…”

Section: In Vitro Fertilization and Capacitation Of Mouse Spermmentioning

confidence: 52%

Effect of capacitation on the endocannabinoid system of mouse sperm

Catanzaro

Battista

Rossi

et al. 2011

Molecular and Cellular Endocrinology

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ABSTRACTThe presence of the elements of the endocannabinoid system (ECS) in sperm isolated from several species (from invertebrates to mammals, humans included) has supported the "evolutionary theory" that proposes endocannabinoids as check points in reproductive events like capacitation. In this study, we characterized the ECS elements at the mRNA, protein and functional levels in mouse sperm before and after capacitation. We found that the latter process increases the endogenous levels of the two major endocannabinoids (anandamide and 2-arachidonoylglycerol), through a decreased degradation and increased biosynthesis, respectively. Additionally, we found that the binding activity of cannabinoid receptors was not affected by sperm capacitation, whereas that of vanilloid receptor was reduced. Overall, our data demonstrate that mouse sperm have a fully functional ECS, and that capacitation alters the endogenous tone of the major endocannabinoids through distinct mechanisms.

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Section: In Vitro Fertilization and Capacitation Of Mouse Spermmentioning

confidence: 52%

Effect of capacitation on the endocannabinoid system of mouse sperm

Catanzaro

Battista

Rossi

et al. 2011

Molecular and Cellular Endocrinology

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“…Cholesterol extraction alters the protein-lipid organization, especially of the sperm head PM, increasing its fluidity and activating a signal transduction pathway that leads to tyrosine phosphorylation of sperm proteins. The probability that cholesterol is a regulator of the AR is exemplified by the promotion of the binding of RAB3A to the sperm PM and the disruption of CAV1 oligomers; both processes are regulated by the loss of cholesterol (Belmonte et al 2005, Sleight et al 2005. Therefore, our initial hypothesis for the regulation of the interaction between CAV1 and CDC42 was that the subtraction of cholesterol by BSA or cyclodextrin might promote the dissociation of these proteins.…”

Section: Discussionmentioning

confidence: 99%

The association between CDC42 and caveolin-1 is involved in the regulation of capacitation and acrosome reaction of guinea pig and mouse sperm

Baltiérrez-Hoyos

Roa-Espitia²,

Hernández‐González³

2012

Reproduction

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In the mammalian sperm, the acrosome reaction (AR) is considered to be a regulated secretion that is an essential requirement for physiological fertilization. The AR is the all-or-nothing secretion system that allows for multiple membrane fusion events. It is a Ca 2C -regulated exocytosis reaction that has also been shown to be regulated by several signaling pathways. CDC42 has a central role in the regulated exocytosis through the activation of SNARE proteins and actin polymerization. Furthermore, the lipid raft protein caveolin-1 (CAV1) functions as a scaffold and guanine nucleotide dissociation inhibitor protein for CDC42, which is inactivated when associated with CAV1. CDC42 and other RHO proteins have been shown to localize in the acrosome region of mammalian sperm; however, their relationship with the AR is unknown. Here, we present the first evidence that CDC42 and CAV1 could be involved in the regulation of capacitation and the AR. Our findings show that CDC42 is activated early during capacitation, reaching an activation maximum after 20 min of capacitation. Spontaneous and progesterone-induced ARs were inhibited when sperm were capacitated in presence of secramine A, a specific CDC42 inhibitor. CAV1 and CDC42 were co-immunoprecipitated from the membranes of noncapacitated sperm; this association was reduced in capacitated sperm, and our data suggest that the phosphorylation (Tyr14) of CAV1 by c-Src is involved in such reductions. We suggest that CDC42 activation is favored by the disruption of the CAV1-CDC42 interaction, allowing for its participation in the regulation of capacitation and the AR.

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“…1B, only capacitated cells responded to S1P (CAPϩS1P and NON CAPϩS1P). We also treated sperm cells with 15 M progesterone to assess their capacitation status (33,34) …”

Section: Sphingosine 1-phosphate Triggersmentioning

confidence: 99%

Sphingosine 1-Phosphate and Sphingosine Kinase Are Involved in a Novel Signaling Pathway Leading to Acrosomal Exocytosis

Suhaiman

Blas

Obeid

et al. 2010

Journal of Biological Chemistry

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Regulated secretion is a central issue for the specific function of many cells; for instance, mammalian sperm acrosomal exocytosis is essential for egg fertilization. Sphingosine 1-phosphate is a bioactive sphingolipid that regulates crucial physiological processes. Here we report that this lipid triggers acrosomal exocytosis in human sperm by a mechanism involving a G i -coupled receptor. Real-time imaging showed a remarkable increase of cytosolic calcium upon activation with sphingosine 1-phosphate and pharmacological experiments indicate that the process requires extracellular calcium influx through voltage and store-operated calcium channels and efflux from intracellular stores through inositol 1,4,5-trisphosphate-sensitive calcium channels. Sphingosine 1-phosphate-induced exocytosis requires phospholipase C and protein kinase C activation. We investigated possible sources of the lipid. Western blot indicates that sphingosine kinase 1 is present in spermatozoa. Indirect immunofluorescence showed that phorbol ester, a potent protein kinase C activator that can also trigger acrosomal exocytosis, redistributes sphingosine kinase 1 to the acrosomal region. Functional assays showed that phorbol ester-induced exocytosis depends on the activation of sphingosine kinase 1. Furthermore, incorporation of 32 P to sphingosine demonstrates that cells treated with the phorbol ester increase their sphingosine kinase activity that yields sphingosine 1-phosphate. We present here the first evidence indicating that human spermatozoa produce sphingosine 1-phosphate when challenged with an exocytic stimulus. These observations point to a new role of sphingosine 1-phosphate in a signaling cascade that facilitates acrosome reaction providing some clues about novel lipid molecules involved in exocytosis.Sphingosine 1-phosphate (S1P) 2 is a bioactive sphingolipid metabolite that regulates a variety of cellular processes. For years, researchers thought that the biological effects of S1P were due to its actions as an intracellular second messenger. However, surface receptors have recently been identified, and, since then, many downstream effects of S1P receptor activation have been demonstrated (1).

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Cholesterol content regulates acrosomal exocytosis by enhancing Rab3A plasma membrane association

Cited by 56 publications

References 62 publications

Effect of capacitation on the endocannabinoid system of mouse sperm

Effect of capacitation on the endocannabinoid system of mouse sperm

The association between CDC42 and caveolin-1 is involved in the regulation of capacitation and acrosome reaction of guinea pig and mouse sperm

Sphingosine 1-Phosphate and Sphingosine Kinase Are Involved in a Novel Signaling Pathway Leading to Acrosomal Exocytosis

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