title: Breast cancer resistance protein regulates apical ectoplasmic specialization dynamics stage specifically in the rat testis.
abstract: Drug transporters determine the bioavailability of drugs in the testis behind the blood-testis barrier (BTB). Thus, they are crucial for male contraceptive development if these drugs (e.g., adjudin) exert their effects behind the BTB. Herein breast cancer resistance protein (Bcrp), an efflux drug transporter, was found to be expressed by both Sertoli and germ cells. Interestingly, Bcrp was not a component of the Sertoli cell BTB. Instead, it was highly expressed by peritubular myoid cells at the tunica propria and also endothelial cells of the microvessels in the interstitium at all stages of the epithelial cycle. Unexpectedly, Bcrp was found to be expressed at the Sertoli-step 18-19 spermatid interface but limited to stage VI-early VIII tubules, and an integrated component of the apical ectoplasmic specialization (apical ES). Apparently, Bcrp is being used by late-stage spermatids to safeguard their completion of spermiogenesis by preventing harmful drugs to enter these cells while they transform to spermatozoa. Also, the association of Bcrp with actin, Eps8 (epidermal growth factor receptor pathway substrate 8, an actin barbed end capping and bundling protein), and Arp3 (actin-related protein 3, a component of the Arp2/3 complex known to induce branched actin polymerization) at the apical ES suggest that Bcrp may be involved in regulating the organization of actin filament bundles at the site. Indeed, a knockdown of Bcrp by RNAi in the testis perturbed the apical ES function, disrupting spermatid polarity and adhesion. In summary, Bcrp is a regulator of the F-actin-rich apical ES in the testis.
authors: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, NY 10065, USA.
authors: Xiaojing
authors: X
authors: Qian
authors: Dolores D
authors: DD
authors: Mruk
authors: Elissa W P
authors: EW
authors: Wong
authors: C Yan
authors: CY
authors: Cheng
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051378:Actin-Related Protein 3 / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001814:Blood-Testis Barrier / Q000378:metabolism*; D003272:Contraceptive Agents, Male / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006834:Hydrazines / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D055806:Microvessels / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012670:Seminiferous Epithelium / Q000166:cytology / Q000378:metabolism*; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism*; D013087:Spermatids / Q000166:cytology / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism*
chemical_list: C432482:1-(2,4-dichlorobenzyl)indazole-3-carbohydrazide; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C489249:Abcg2 protein, rat; D051378:Actin-Related Protein 3; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D003272:Contraceptive Agents, Male; C498142:Eps8 protein, rat; D006834:Hydrazines; D007191:Indazoles; D012333:RNA, Messenger
references: Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11411-6
references: 20534520
references: Adv Exp Med Biol. 2008;636:212-33
references: 19856170
references: Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9657-62
references: 18621709
references: J Natl Cancer Inst. 1999 Mar 3;91(5):429-33
references: 10070941
references: Int J Biochem Cell Biol. 2009 Dec;41(12):2578-87
references: 19720156
references: Nat Commun. 2012;3:1185
references: 23149730
references: Methods Mol Biol. 2011;763:237-52
references: 21874456
references: Trends Pharmacol Sci. 2011 Feb;32(2):99-106
references: 21168226
references: Int Rev Cytol. 1985;94:177-211
references: 3894273
references: Bioessays. 2004 Sep;26(9):978-92
references: 15351968
references: FASEB J. 2009 Aug;23(8):2555-67
references: 19293393
references: Biol Reprod. 1971 Apr;4(2):195-215
references: 4107186
references: FASEB J. 2013 Feb;27(2):464-77
references: 23073828
references: Mol Pharmacol. 2007 Oct;72(4):967-75
references: 17644650
references: Tissue Cell. 1977;9(3):475-98
references: 929577
references: Prog Histochem Cytochem. 2011 Aug;46(2):49-127
references: 21705043
references: J Cell Physiol. 1996 Jul;168(1):123-33
references: 8647906
references: Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15665-70
references: 9861027
references: Endocrinology. 2012 Oct;153(10):5036-48
references: 22948214
references: J Endocrinol. 2011 Jun;209(3):337-51
references: 21471187
references: Biol Reprod. 1990 Sep;43(3):517-24
references: 2271733
references: J Exp Med. 1998 Sep 7;188(5):797-808
references: 9730882
references: Contraception. 2005 Oct;72(4):251-61
references: 16181968
references: Adv Exp Med Biol. 2008;636:186-211
references: 19856169
references: Biochem J. 2011 May 1;435(3):553-62
references: 21486226
references: Mol Cell Endocrinol. 1994 Sep;104(2):213-27
references: 7988748
references: Spermatogenesis. 2011 Apr;1(2):121-122
references: 22319660
references: Pharmacol Rev. 2012 Jan;64(1):16-64
references: 22039149
references: Biochem Pharmacol. 2012 Apr 15;83(8):1084-103
references: 22248732
references: Biol Reprod. 2003 Aug;69(2):656-72
references: 12700184
references: Cell Tissue Res. 2012 Aug;349(2):551-63
references: 22581381
references: Am J Pathol. 1996 Apr;148(4):1237-47
references: 8644864
references: Endocr Rev. 1982 Fall;3(4):404-17
references: 6295753
references: Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11399-404
references: 20534521
references: Adv Exp Med Biol. 2012;763:1-19
references: 23397617
references: Endocr Rev. 1994 Feb;15(1):102-15
references: 8156935
references: Cytoskeleton (Hoboken). 2011 Sep;68(9):471-90
references: 21850706
references: J Reprod Fertil Suppl. 1970;10:105-22
references: 4951168
references: Adv Exp Med Biol. 2012;763:70-84
references: 23397619
references: Anat Rec. 1973 Apr;175(4):639-56
references: 4700664
references: Trends Endocrinol Metab. 2004 Nov;15(9):439-47
references: 15519891
references: Endocrinology. 2012 Dec;153(12):6041-53
references: 23038739
references: Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19623-8
references: 22106313
references: Trends Cell Biol. 2012 Mar;22(3):141-50
references: 22306177
references: Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15649-54
references: 12429862
references: Eur J Cancer. 2004 Sep;40(14):2064-70
references: 15341980
references: Biochem J. 2011 Jan 15;433(2):253-62
references: 21175430
references: Semin Cell Dev Biol. 2010 Jun;21(4):350-6
references: 19913105
references: Adv Exp Med Biol. 2012;763:237-59
references: 23397628
references: Biol Reprod. 1970 Dec;3(3):308-26
references: 4108372
references: Adv Exp Med Biol. 2008;636:1-15
references: 19856159