Novel signaling pathways involved in sperm acquisition of fertilizing capacity

Visconti, Pablo E.; Westbrook, V. Anne; Chertihin, Olga; Demarco, Ignacio A.; Sleight, Susan B.; Diekman, Alan B.

doi:10.1016/s0165-0378(01)00103-6

Cited by 304 publications

(252 citation statements)

References 89 publications

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“…The change in overall mechanoelastic properties of the cell may be directly responsible. Spermatozoa are examples of flagellated cells that undergo changes in membrane fluidity concurrent with the onset of hypermotility (33). In these cells, hyperactivation is associated with an efflux of cholesterol and an increase in membrane fluidity.…”

Section: Discussionmentioning

confidence: 99%

The Plasma Membrane of Bloodstream-form African Trypanosomes Confers Susceptibility and Specificity to Killing by Hydrophobic Peptides

Harrington

Widener

Stephens

et al. 2010

Journal of Biological Chemistry

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Trypanosoma brucei is the causative agent of both a veterinary wasting disease and human African trypanosomiasis, or sleeping sickness. The cell membrane of the developmental stage found within the mammalian host, the bloodstream form (BSF), is highly dynamic, exhibiting rapid rates of endocytosis and lateral flow of glycosylphosphatidylinositol-anchored proteins. Here, we show that the cell membrane of these organisms is a target for killing by small hydrophobic peptides that increase the rigidity of lipid bilayers. Specifically, we have derived trypanocidal peptides that are based upon the hydrophobic N-terminal signal sequences of human apolipoproteins. These peptides selectively partitioned into the plasma membrane of BSF trypanosomes, resulting in an increase in the rigidity of the bilayer, dramatic changes in cell motility, and subsequent cell death. No killing of the developmental stage found within the insect midgut, the procyclic form, was observed. Additionally, the peptides exhibited no toxicity toward mammalian cell lines and did not induce hemolysis. Studies with model liposomes indicated that bilayer fluidity dictates the susceptibility of membranes to manipulation by hydrophobic peptides. We suggest that the composition of the BSF trypanosome cell membrane confers a high degree of fluidity and unique susceptibility to killing by hydrophobic peptides and is therefore a target for the development of trypanocidal drugs.

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Section: Discussionmentioning

confidence: 99%

The Plasma Membrane of Bloodstream-form African Trypanosomes Confers Susceptibility and Specificity to Killing by Hydrophobic Peptides

Harrington

Widener

Stephens

et al. 2010

Journal of Biological Chemistry

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“…De fato, maiores porcentuais (P<0,05) de espermatozóides móveis (73,7%±0,99) foram verificados nas doses seminais contendo BSA comparadas às processadas sem BSA (62,5%±1,53), considerando a média de todos os momentos de avaliação. Por sua vez, sabe-se que a BSA está envolvida na remoção do colesterol da membrana espermática e conseqüentemente na alteração na permeabilidade desta, facilitando a capacitação espermática in vitro (Yanagimachi, 1989;Visconti et al, 2002). Assim, a facilitação da capacitação também poderia explicar a maior capacidade de ligação dos espermatozóides visto que o substrato sintético simula o papel da zona pelúcida na interação espermatozóide-ovócito.…”

Section: Resultsunclassified

Fertilidade de sêmen suíno avaliada pelo teste de ligação dos espermatozóides a um substrato sintético

Reis

Bernardi

Wentz

et al. 2003

Pesq. agropec. bras.

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Resumo -O objetivo deste trabalho foi avaliar a fertilidade de sêmen suíno pelo teste de ligação de espermatozóides a um substrato sintético. A motilidade (MOT) e o porcentual de espermatozóides ligados (PEL) foram avaliados após 5, 24, 48 e 72 horas de armazenamento a 17ºC. O PEL foi determinado em soluções contendo 6,25 ou 12,5 milhões de espermatozóides/mL, com ou sem albumina sérica bovina (BSA), preparadas a partir de dois a cinco ejaculados de cada um dos quatro machos. Cinqüenta e oito leitoas foram inseminadas, uma vez, 24 horas após o início do estro. Houve correlação positiva (P = 0,0001; r = 0,33) entre a MOT e o PEL. O PEL foi maior com 12,5 milhões de espermatozóides/mL e na presença de BSA (P<0,05). Após 72 horas, o macho 3 apresentou PEL inferior ao dos outros três (P<0,05). As taxas de clivagem (TC) e de embriões morfologicamente normais não diferiram entre indivíduos, mas o macho 3 apresentou menos de 70,0% de TC no quartil superior, enquanto os outros tiveram mais de 75,0%. Os machos diferem quanto à capacidade de ligação de seus espermatozóides ao substrato sintético, a partir de 24 horas de armazenamento do sêmen. A ligação dos espermatozóides ao substrato sintético é maior com a inclusão de BSA e com o aumento da concentração espermática.Termos para indexação: albumina sérica, inseminação artificial, ligação espermatozóide-ovócito. Boar semen fertility evaluated by a sperm-binding assay to a synthetic substrateAbstract -The objective of this work was to evaluate boar semen fertility by a sperm-binding assay to a synthetic substrate. Motility (MOT) and percentage of bound sperm (PSB) were evaluated after 5, 24, 48 and 72 hours of storage at 17°C. PSB was analyzed in solutions containing 6.25 or 12.5 million of spermatozoa/mL, with or without bovine serum albumin (BSA), processed from two to five ejaculates of four boars. Fifty eight gilts were inseminated, a single time, 24 hours after the beginning of estrus. There was a positive correlation (P = 0.0001; r = 0.33) between MOT and PSB. Higher percentages of PSB were observed with 12.5 million of spermatozoa/mL and in the presence of BSA (P<0.05). After 72 hours, boar 3 showed lower PSB (P<0.05) than the other boars. The cleavage (TC) and normal embryo rates did not differ among boars, but boar 3 showed less than 70.0% of TC belonging to the superior quartile while boars 1, 2 and 4 had more than 75.0%. After 24 hours of sperm storage, boars differ in their sperm binding to the synthetic substrate. Binding of swine spermatozoa to the synthetic substrate is higher in the presence of BSA and with the increase of spermatic concentration.

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“…During capacitation, mammalian sperm lose cholesterol from their membranes. Bovine serum albumin, cyclodextrins, and HDL are all capable of binding cholesterol and increasing the rate of capacitation (1). In mammalian sperm, no mechanism has been described for cholesterol removal from membranes.…”

Section: Resultsmentioning

confidence: 99%

“…Upon release into seawater, sea urchin sperm activate motility and, before fusing with eggs, undergo the exocytotic acrosome reaction (AR). 1 In mammals, this process is further complicated by the need to undergo capacitation before the AR can be triggered. Capacitation is a poorly understood process involving cholesterol efflux, changes in intracellular ion concentrations, and tyrosine phosphorylation (1).…”

mentioning

confidence: 99%

“…1 In mammals, this process is further complicated by the need to undergo capacitation before the AR can be triggered. Capacitation is a poorly understood process involving cholesterol efflux, changes in intracellular ion concentrations, and tyrosine phosphorylation (1). All of these processes involve changes in membrane structure and composition (2), and the molecules involved in these changes are only now being discovered.…”

mentioning

confidence: 99%

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An ATP-binding Cassette Transporter Is a Major Glycoprotein of Sea Urchin Sperm Membranes

Mengerink

Vacquier

2002

Journal of Biological Chemistry

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Sperm are terminally differentiated cells that undergo several membrane-altering events before fusion with eggs. One event, the sea urchin sperm acrosome reaction (AR), is blocked by the lectin wheat germ agglutinin (WGA). In an effort to identify proteins involved in the AR induction, the peptide sequence was obtained from a 220-kDa WGA-binding protein. Degenerate PCR and library screening resulted in the full-length deduced amino acid sequence of an ATP-binding cassette transporter, suABCA. The protein of 1,764 residues has two transmembrane regions, two nucleotide-binding domains, and is most closely related to the human ABC subfamily A member 3 transporter (ABCA3). Sequence analysis suggests a large extracellular loop between transmembrane spanning segments 7 and 8, with five N-linked glycosylation sites. An antibody made to the loop region binds to non-permeabilized cells, supporting that this region is extracellular. suABCA is found in sperm membrane vesicles, it can be solubilized with nonionic detergents, and it shifts from 220 to 200 kDa upon protein:N-glycanase F digestion. suABCA localizes to the entire surface of sperm in a punctate pattern, but is not detected in lipid rafts. Based on its relationship to subfamily A, suABCA is most likely involved in phospholipid or cholesterol transport. This is the first investigation of an ABC transporter in animal sperm.

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Novel signaling pathways involved in sperm acquisition of fertilizing capacity

Cited by 304 publications

References 89 publications

The Plasma Membrane of Bloodstream-form African Trypanosomes Confers Susceptibility and Specificity to Killing by Hydrophobic Peptides

The Plasma Membrane of Bloodstream-form African Trypanosomes Confers Susceptibility and Specificity to Killing by Hydrophobic Peptides

Fertilidade de sêmen suíno avaliada pelo teste de ligação dos espermatozóides a um substrato sintético

An ATP-binding Cassette Transporter Is a Major Glycoprotein of Sea Urchin Sperm Membranes

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