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New insights into the regulation of cholesterol efflux from the sperm membrane.

Leahy T, Gadella BM - Asian J. Androl. (2015 Jul-Aug)

Bottom Line: How does a hydrophobic cholesterol molecule inserted in the sperm plasma membrane enter the energetically unfavorable aqueous surroundings?The overall aim is to better understand cholesterol redistribution in the sperm plasma membrane, its relation to the possible activation of a cholesterol transporter and the role of cholesterol acceptors.Armed with such knowledge, sperm handling techniques can be adapted to better prepare spermatozoa for in vitro and in vivo fertilization.

View Article: PubMed Central - PubMed

Affiliation: Department of Farm Animal Health and of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 2, 3584 CM Utrecht, The Netherlands.

ABSTRACT
Cholesterol is an essential component of the mammalian plasma membrane because it promotes membrane stability without comprising membrane fluidity. Given this important cellular role, cholesterol levels are tightly controlled at multiple levels. It has been clearly shown that cholesterol redistribution and depletion from the sperm membrane is a key part of the spermatozoon's preparation for fertilization. Some factors that regulate these events are described (e.g., bicarbonate, calcium) but the mechanisms underlying cholesterol export are poorly understood. How does a hydrophobic cholesterol molecule inserted in the sperm plasma membrane enter the energetically unfavorable aqueous surroundings? This review will provide an overview of knowledge in this area and highlight our gaps in understanding. The overall aim is to better understand cholesterol redistribution in the sperm plasma membrane, its relation to the possible activation of a cholesterol transporter and the role of cholesterol acceptors. Armed with such knowledge, sperm handling techniques can be adapted to better prepare spermatozoa for in vitro and in vivo fertilization.

No MeSH data available.


Reverse cholesterol transport (RCT) from the sperm membrane to high-density lipoproteins (HDL). ATP binding cassette (ABC) transporters can transport free sterols to acceptor proteins like HDL, which are abundant in the oviduct. The apolipoprotein A1 protein forms a circular dimer and stabilises discoidal, nascent HDL (mainly composed of phospholipids and free cholesterol). This structure can import more free cholesterol and phospholipids into its bilayer or esterify the free cholesterol with diacylglycerol to neutralize the lipids for intracellular storage (triacylglycerol in black and cholesteryl esters with the fatty acid esterified in red). The origin of the fatty acids used to esterify cholesterol in the oviduct is not known. See introduction and Figure 1 for information on Lo and Ld. Note that by analogy with other cell types, the ABC transporters are drawn in this model in the Lo microdomains.52 This model also presents the possibility that after export of cholesterol in the Lo regions, the vacant space for cholesterol is filled in by attracting cholesterol from Ld to explain why sperm RCT does not lead to disruption of aggregated Lo microdomains as observed in other cell types.95
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Figure 3: Reverse cholesterol transport (RCT) from the sperm membrane to high-density lipoproteins (HDL). ATP binding cassette (ABC) transporters can transport free sterols to acceptor proteins like HDL, which are abundant in the oviduct. The apolipoprotein A1 protein forms a circular dimer and stabilises discoidal, nascent HDL (mainly composed of phospholipids and free cholesterol). This structure can import more free cholesterol and phospholipids into its bilayer or esterify the free cholesterol with diacylglycerol to neutralize the lipids for intracellular storage (triacylglycerol in black and cholesteryl esters with the fatty acid esterified in red). The origin of the fatty acids used to esterify cholesterol in the oviduct is not known. See introduction and Figure 1 for information on Lo and Ld. Note that by analogy with other cell types, the ABC transporters are drawn in this model in the Lo microdomains.52 This model also presents the possibility that after export of cholesterol in the Lo regions, the vacant space for cholesterol is filled in by attracting cholesterol from Ld to explain why sperm RCT does not lead to disruption of aggregated Lo microdomains as observed in other cell types.95

Mentions: Supporting evidence can be found in the literature on the distinction between Lo and Ld domains for ABC transporters52 (Figure 3). ABC transporters on spermatozoa are predominantly present in the apical area of the head. This coincides with the area of raft aggregation (Lo) upon in vitro capacitation and the clustering and depletion of cholesterol in capacitated spermatozoa.225354 This formation is dependent on bicarbonate-mediated sperm signaling, and, as both PKA and protein tyrosine kinases are activated55 it is possible that altered phosphorylation of the cholesterol transporters changes their actions in cholesterol transport.51 Interestingly, ABCG1 has been described to become tyrosine phosphorylated after interaction with caveolin-1 (a membrane raft marker), and both were required to regulate cholesterol efflux from HEK293 cells to ApoA1.56


New insights into the regulation of cholesterol efflux from the sperm membrane.

Leahy T, Gadella BM - Asian J. Androl. (2015 Jul-Aug)

Reverse cholesterol transport (RCT) from the sperm membrane to high-density lipoproteins (HDL). ATP binding cassette (ABC) transporters can transport free sterols to acceptor proteins like HDL, which are abundant in the oviduct. The apolipoprotein A1 protein forms a circular dimer and stabilises discoidal, nascent HDL (mainly composed of phospholipids and free cholesterol). This structure can import more free cholesterol and phospholipids into its bilayer or esterify the free cholesterol with diacylglycerol to neutralize the lipids for intracellular storage (triacylglycerol in black and cholesteryl esters with the fatty acid esterified in red). The origin of the fatty acids used to esterify cholesterol in the oviduct is not known. See introduction and Figure 1 for information on Lo and Ld. Note that by analogy with other cell types, the ABC transporters are drawn in this model in the Lo microdomains.52 This model also presents the possibility that after export of cholesterol in the Lo regions, the vacant space for cholesterol is filled in by attracting cholesterol from Ld to explain why sperm RCT does not lead to disruption of aggregated Lo microdomains as observed in other cell types.95
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492045&req=5

Figure 3: Reverse cholesterol transport (RCT) from the sperm membrane to high-density lipoproteins (HDL). ATP binding cassette (ABC) transporters can transport free sterols to acceptor proteins like HDL, which are abundant in the oviduct. The apolipoprotein A1 protein forms a circular dimer and stabilises discoidal, nascent HDL (mainly composed of phospholipids and free cholesterol). This structure can import more free cholesterol and phospholipids into its bilayer or esterify the free cholesterol with diacylglycerol to neutralize the lipids for intracellular storage (triacylglycerol in black and cholesteryl esters with the fatty acid esterified in red). The origin of the fatty acids used to esterify cholesterol in the oviduct is not known. See introduction and Figure 1 for information on Lo and Ld. Note that by analogy with other cell types, the ABC transporters are drawn in this model in the Lo microdomains.52 This model also presents the possibility that after export of cholesterol in the Lo regions, the vacant space for cholesterol is filled in by attracting cholesterol from Ld to explain why sperm RCT does not lead to disruption of aggregated Lo microdomains as observed in other cell types.95
Mentions: Supporting evidence can be found in the literature on the distinction between Lo and Ld domains for ABC transporters52 (Figure 3). ABC transporters on spermatozoa are predominantly present in the apical area of the head. This coincides with the area of raft aggregation (Lo) upon in vitro capacitation and the clustering and depletion of cholesterol in capacitated spermatozoa.225354 This formation is dependent on bicarbonate-mediated sperm signaling, and, as both PKA and protein tyrosine kinases are activated55 it is possible that altered phosphorylation of the cholesterol transporters changes their actions in cholesterol transport.51 Interestingly, ABCG1 has been described to become tyrosine phosphorylated after interaction with caveolin-1 (a membrane raft marker), and both were required to regulate cholesterol efflux from HEK293 cells to ApoA1.56

Bottom Line: How does a hydrophobic cholesterol molecule inserted in the sperm plasma membrane enter the energetically unfavorable aqueous surroundings?The overall aim is to better understand cholesterol redistribution in the sperm plasma membrane, its relation to the possible activation of a cholesterol transporter and the role of cholesterol acceptors.Armed with such knowledge, sperm handling techniques can be adapted to better prepare spermatozoa for in vitro and in vivo fertilization.

View Article: PubMed Central - PubMed

Affiliation: Department of Farm Animal Health and of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 2, 3584 CM Utrecht, The Netherlands.

ABSTRACT
Cholesterol is an essential component of the mammalian plasma membrane because it promotes membrane stability without comprising membrane fluidity. Given this important cellular role, cholesterol levels are tightly controlled at multiple levels. It has been clearly shown that cholesterol redistribution and depletion from the sperm membrane is a key part of the spermatozoon's preparation for fertilization. Some factors that regulate these events are described (e.g., bicarbonate, calcium) but the mechanisms underlying cholesterol export are poorly understood. How does a hydrophobic cholesterol molecule inserted in the sperm plasma membrane enter the energetically unfavorable aqueous surroundings? This review will provide an overview of knowledge in this area and highlight our gaps in understanding. The overall aim is to better understand cholesterol redistribution in the sperm plasma membrane, its relation to the possible activation of a cholesterol transporter and the role of cholesterol acceptors. Armed with such knowledge, sperm handling techniques can be adapted to better prepare spermatozoa for in vitro and in vivo fertilization.

No MeSH data available.