Membrane rafts regulate phospholipase B activation in murine sperm

Asano, Atsushi; Nelson-Harrington, Jacquelyn L.; Travis, Alexander J.

doi:10.4161/cib.27362

Cited by 6 publications

(4 citation statements)

References 20 publications

(27 reference statements)

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“…PLB1 was originally identified in humans by its expression in the epidermis and suggested to function by promoting the skin barrier function by breakdown of lipids into free fatty acids 111 . In addition, based on its role in promoting acrosome exocytosis in sperm 112 – 114 , there is a possibility that it could function to modulate secretory processes in other situations such as sweating. On the other hand, PPP1CB encodes the beta-subunit of the Serine/threonine-protein phosphatase PP1, which is a key enzyme involved in the regulation of a large number of cellular processes 115 .…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study in Japanese females identifies fifteen novel skin-related trait associations

Endo

Johnson

Morino³

et al. 2018

Sci Rep

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Skin trait variation impacts quality-of-life, especially for females from the viewpoint of beauty. To investigate genetic variation related to these traits, we conducted a GWAS of various skin phenotypes in 11,311 Japanese women and identified associations for age-spots, freckles, double eyelids, straight/curly hair, eyebrow thickness, hairiness, and sweating. In silico annotation with RoadMap Epigenomics epigenetic state maps and colocalization analysis of GWAS and GTEx Project eQTL signals provided information about tissue specificity, candidate causal variants, and functional target genes. Novel signals for skin-spot traits neighboured AKAP1/MSI2 (rs17833789; P = 2.2 × 10−9), BNC2 (rs10810635; P = 2.1 × 10−22), HSPA12A (rs12259842; P = 7.1 × 10−11), PPARGC1B (rs251468; P = 1.3 × 10−21), and RAB11FIP2 (rs10444039; P = 5.6 × 10−21). HSPA12A SNPs were the only protein-coding gene eQTLs identified across skin-spot loci. Double edged eyelid analysis identified that a signal around EMX2 (rs12570134; P = 8.2 × 10−15) was also associated with expression of EMX2 and the antisense-RNA gene EMX2OS in brain putamen basal ganglia tissue. A known hair morphology signal in EDAR was associated with both eyebrow thickness (rs3827760; P = 1.7 × 10−9) and straight/curly hair (rs260643; P = 1.6 × 10−103). Excessive hairiness signals’ top SNPs were also eQTLs for TBX15 (rs984225; P = 1.6 × 10−8), BCL2 (rs7226979; P = 7.3 × 10−11), and GCC2 and LIMS1 (rs6542772; P = 2.2 × 10−9). For excessive sweating, top variants in two signals in chr2:28.82-29.05 Mb (rs56089836; P = 1.7 × 10−11) were eQTLs for either PPP1CB or PLB1, while a top chr16:48.26–48.45 Mb locus SNP was a known ABCC11 missense variant (rs6500380; P = 6.8 × 10−10). In total, we identified twelve loci containing sixteen association signals, of which fifteen were novel. These findings will help dermatologic researchers better understand the genetic underpinnings of skin-related phenotypic variation in human populations.

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Section: Discussionmentioning

confidence: 99%

Genome-wide association study in Japanese females identifies fifteen novel skin-related trait associations

Endo

Johnson

Morino³

et al. 2018

Sci Rep

View full text Add to dashboard Cite

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“…Interestingly, the association of CDC42 and the oligomerization of caveolin-1 have been described (Baltiérrez-Hoyos et al 2012 ) and also, the involvement of CDC42 in lipid raft-mediated synaptic delivery has recently been reported (Brachet et al 2015 ). These, together with the recruitment of Rab 3A to the plasma membrane (Belmonte et al 2005 ) and the finding that phospholipase B is activated after reverse cholesterol transport from murine sperm (Asano et al 2013a , b ) are all preparative steps for the acrosome reaction that deserves more research attention. The capacitation-dependent formation of zona pellucida and/or cumulus binding protein complexes as well as the docking of the acrosome make sperm prepared to correctly interact with the cumulus and zona pellucida.…”

Section: Discussionmentioning

confidence: 99%

Ultrastructure and lipid composition of detergent-resistant membranes derived from mammalian sperm and two types of epithelial cells

et al. 2015

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Lipid rafts are micro-domains of ordered lipids (Lo phase) in biological membranes. The Lo phase of cellular membranes can be isolated from disordered lipids (Ld phase) after treatment with 1 % Triton X-100 at 4 °C in which the Lo phase forms the detergent-resistant membrane (DRM) fraction. The lipid composition of DRM derived from Madin-Darby canine kidney (MDCK) cells, McArdle cells and porcine sperm is compared with that of the whole cell. Remarkably, the unsaturation and chain length degree of aliphatic chains attached to phospholipids is virtually the same between DRM and whole cells. Cholesterol and sphingomyelin were enriched in DRMs but to a cell-specific molar ratio. Sulfatides (sphingolipids from MDCK cells) were enriched in the DRM while a seminolipid (an alkylacylglycerolipid from sperm) was depleted from the DRM. Treatment with <5 mM methyl-ß-cyclodextrin (MBCD) caused cholesterol removal from the DRM without affecting the composition and amount of the phospholipid while higher levels disrupted the DRM. The substantial amount of (poly)unsaturated phospholipids in DRMs as well as a low stoichiometric amount of cholesterol suggest that lipid rafts in biological membranes are more fluid and dynamic than previously anticipated. Using negative staining, ultrastructural features of DRM were monitored and in all three cell types the DRMs appeared as multi-lamellar vesicular structures with a similar morphology. The detergent resistance is a result of protein–cholesterol and sphingolipid interactions allowing a relatively passive attraction of phospholipids to maintain the Lo phase. For this special issue, the relevance of our findings is discussed in a sperm physiological context.

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“…The inset shows that heat inactivated the calcium-independent PLA 2 activity released in response to capacitating conditions (BC + CD). Panel b adapted from Asano et al (2013a) (2-OHCD), a mediator of sterol efflux. Insignificant activity was released in the presence of bicarbonate alone or in non-capacitated sperm (Fig.…”

Section: Sterol Efflux-mediated Regulation Of Sperm Phospholipidsmentioning

confidence: 99%

Lipid Regulation of Acrosome Exocytosis

Cohen

Mukai

Travis

2016

Advances in Anatomy, Embryology and Cell Biology

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Lipids are critical regulators of mammalian sperm function, first helping prevent premature acrosome exocytosis, then enabling sperm to become competent to fertilize at the right place/time through the process of capacitation, and ultimately triggering acrosome exocytosis. Yet because they do not fit neatly into the "DNA--RNA-protein" synthetic pathway, they are understudied and poorly understood. Here, we focus on three lipids or lipid classes-cholesterol, phospholipids, and the ganglioside G(M1)--in context of the modern paradigm of acrosome exocytosis. We describe how these various- species are precisely segregated into membrane macrodomains and microdomains, simultaneously preventing premature exocytosis while acting as foci for organizing regulatory and effector molecules that will enable exocytosis. Although the mechanisms responsible for these domains are poorly defined, there is substantial evidence for their composition and functions. We present diverse ways that lipids and lipid modifications regulate capacitation and acrosome exocytosis, describing in more detail how removal of cholesterol plays a master regulatory role in enabling exocytosis through at least two complementary pathways. First, cholesterol efflux leads to proteolytic activation of phospholipase B, which cleaves both phospholipid tails. The resultant changes in membrane curvature provide a mechanism for the point fusions now known to occur far before a sperm physically interacts with the zona pellucida. Cholesterol efflux also enables G(M1) to regulate the voltage-dependent cation channel, Ca(V)2.3, triggering focal calcium transients required for acrosome exocytosis in response to subsequent whole-cell calcium rises. We close with a model integrating functions for lipids in regulating acrosome exocytosis.

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Membrane rafts regulate phospholipase B activation in murine sperm

Cited by 6 publications

References 20 publications

Genome-wide association study in Japanese females identifies fifteen novel skin-related trait associations

Genome-wide association study in Japanese females identifies fifteen novel skin-related trait associations

Ultrastructure and lipid composition of detergent-resistant membranes derived from mammalian sperm and two types of epithelial cells

Lipid Regulation of Acrosome Exocytosis

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