Top

Journal of Ovarian Research

Published in:

Open Access 01-12-2015 | Research

Differential expression of lysosome-associated protein transmembrane-4 beta (LAPTM4B) in granulosa cells of ovarian follicles and in other bovine tissues

Authors: Kalidou Ndiaye, Paul D Carrière, Jean Sirois, David W Silversides, Jacques G Lussier

Published in: Journal of Ovarian Research | Issue 1/2015

Abstract

Background

LAPTM4B is a member of the lysosome-associated transmembrane protein superfamily that is differentially expressed in normal human tissues and upregulated in various types of carcinomas. These proteins are thought to be involved in the regulation of cell proliferation and survival. The objective of this study was to investigate the expression of bovine LAPTM4B during ovarian follicular development and in various bovine tissues.

Methods and results

Northern blot analysis revealed a 1.8 kb transcript, with highly variable steady state levels among tissues. RT-PCR analysis showed that LAPTM4B mRNA transcripts were low in granulosa cells of small antral follicles, increased in large dominant follicles, and decreased in ovulatory follicles following injection of human chorionic gonadotropin (hCG; P < 0.003). Ovulatory follicles collected at various times after hCG injection revealed a significant reduction of LAPTM4B mRNA starting at 18 h post-hCG (P < 0.029). Immunobloting analysis using antibodies generated against bovine LAPTM4B recognized proteins of 26.3 and 31.5 kDa in granulosa cells of developing follicles and corpus luteum. Further analyses of affinity-purified His-tag LAPTM4B overexpressed in HEK cells showed that the 31.5 kDa protein represented the ubiquinated isoform of the 26.3 kDa native protein. The 26.3 kDa protein was differentially expressed showing highest amounts in dominant follicles and lowest amounts in ovulatory follicles 24 h post-hCG. Immunohistochemical analyses of LAPTM4B showed marked heterogeneity of labeling signal among tissues, with LAPTM4B mainly localized to perinuclear vesicles, in keeping with its putative lysosomal membrane localization.

Conclusion

This study reports for the first time that bovine LAPTM4B in granulosa cells is present in both unubiquinated and ubiquinated forms, and is differentially expressed in developing ovarian follicles, suggesting a possible role in terminal follicular growth.

Adra CN, Zhu S, Ko JL, Guillemot JC, Cuervo AM, Kobayashi H, et al. LAPTM5: a novel lysosomal-associated multispanning membrane protein preferentially expressed in hematopoietic cells. Genomics. 1996;35(2):328–37.CrossRefPubMed

Cabrita MA, Hobman TC, Hogue DL, King KM, Cass CE. Mouse transporter protein, a membrane protein that regulates cellular multidrug resistance, is localized to lysosomes. Cancer Res. 1999;59(19):4890–7.PubMed

Hogue DL, Nash C, Ling V, Hobman TC. Lysosome-associated protein transmembrane 4 alpha (LAPTM4 alpha) requires two tandemly arranged tyrosine-based signals for sorting to lysosomes. Biochem J. 2002;365(Pt 3):721–30.PubMedCentralPubMed

Hogue DL, Ellison MJ, Young JD, Cass CE. Identification of a novel membrane transporter associated with intracellular membranes by phenotypic complementation in the yeast Saccharomyces cerevisiae. J Biol Chem. 1996;271(16):9801–8.CrossRefPubMed

Marks MS, Woodruff L, Ohno H, Bonifacino JS. Protein targeting by tyrosine- and di-leucine-based signals: evidence for distinct saturable components. J Cell Biol. 1996;135(2):341–54.CrossRefPubMed

Gough NR, Zweifel ME, Martinez-Augustin O, Aguilar RC, Bonifacino JS, Fambrough DM. Utilization of the indirect lysosome targeting pathway by lysosome-associated membrane proteins (LAMPs) is influenced largely by the C-terminal residue of their GYXXphi targeting signals. J Cell Sci. 1999;112(Pt 23):4257–69.PubMed

Cherqui S, Kalatzis V, Trugnan G, Antignac C. The targeting of cystinosin to the lysosomal membrane requires a tyrosine-based signal and a novel sorting motif. J Biol Chem. 2001;276(16):13314–21.CrossRefPubMed

Milkereit R, Rotin D. A role for the ubiquitin ligase Nedd4 in membrane sorting of LAPTM4 proteins. PLoS One. 2011;6(11):e27478.CrossRefPubMedCentralPubMed

Liu J, Zhou R, Zhang N, Rui J, Jin C. Biological function of a novel gene overexpressed in human hepatocellular carcinoma. Chin Med J. 2000;113(10):881–5.PubMed

10.

Shao GZ, Zhou RL, Zhang QY, Zhang Y, Liu JJ, Rui JA, et al. Molecular cloning and characterization of LAPTM4B, a novel gene upregulated in hepatocellular carcinoma. Oncogene. 2003;22(32):5060–9.CrossRefPubMed

11.

He J, Shao G, Zhou R. Effects of the novel gene, LAPTM4B, highly expression in hepatocellular carcinoma on cell proliferation and tumorigenesis of NIH3T3 cells. Beijing da xue xue bao Yi xue ban = Journal of Peking University Health sciences. 2003;35(4):348–52.PubMed

12.

Liu XR, Zhou RL, Zhang QY, Zhang Y, Jin YY, Lin M, et al. Structure analysis and expressions of a novel tetratransmembrane protein, lysosoma-associated protein transmembrane 4 beta associated with hepatocellular carcinoma. World J Gastroenterol. 2004;10(11):1555–9.PubMed

13.

Kasper G, Vogel A, Klaman I, Grone J, Petersen I, Weber B, et al. The human LAPTM4b transcript is upregulated in various types of solid tumours and seems to play a dual functional role during tumour progression. Cancer Lett. 2005;224(1):93–103.CrossRefPubMed

14.

Morris DG, Musat M, Czirjak S, Hanzely Z, Lillington DM, Korbonits M, et al. Differential gene expression in pituitary adenomas by oligonucleotide array analysis. Eur J Endocrinol/European Federation of Endocrine Societies. 2005;153(1):143–51.CrossRef

15.

Li Y, Zhang Q, Tian R, Wang Q, Zhao JJ, Iglehart JD, et al. Lysosomal transmembrane protein LAPTM4B promotes autophagy and tolerance to metabolic stress in cancer cells. Cancer Res. 2011;71(24):7481–9.CrossRefPubMedCentralPubMed

16.

Mihm M, Bleach EC. Endocrine regulation of ovarian antral follicle development in cattle. Anim Reprod Sci. 2003;78(3–4):217–37.CrossRefPubMed

17.

Ginther OJ, Beg MA, Bergfelt DR, Donadeu FX, Kot K. Follicle selection in monovular species. Biol Reprod. 2001;65(3):638–47.CrossRefPubMed

18.

Webb R, Nicholas B, Gong JG, Campbell BK, Gutierrez CG, Garverick HA, et al. Mechanisms regulating follicular development and selection of the dominant follicle. Reprod Suppl. 2003;61:71–90.PubMed

19.

Milvae RA, Hinckley ST, Carlson JC. Luteotropic and luteolytic mechanisms in the bovine corpus luteum. Theriogenology. 1996;45(7):1327–49.CrossRefPubMed

20.

Knight PG, Glister C. Potential local regulatory functions of inhibins, activins and follistatin in the ovary. Reproduction. 2001;121(4):503–12.CrossRefPubMed

21.

Eppig JJ, Wigglesworth K, Pendola FL. The mammalian oocyte orchestrates the rate of ovarian follicular development. Proc Natl Acad Sci U S A. 2002;99(5):2890–4.CrossRefPubMedCentralPubMed

22.

Rosenfeld CS, Wagner JS, Roberts RM, Lubahn DB. Intraovarian actions of oestrogen. Reproduction. 2001;122(2):215–26.CrossRefPubMed

23.

Ndiaye K, Fayad T, Silversides DW, Sirois J, Lussier JG. Identification of downregulated messenger RNAs in bovine granulosa cells of dominant follicles following stimulation with human chorionic gonadotropin. Biol Reprod. 2005;73(2):324–33.CrossRefPubMed

24.

Espey LL, Richards JS. Temporal and spatial patterns of ovarian gene transcription following an ovulatory dose of gonadotropin in the rat. Biol Reprod. 2002;67(6):1662–70.CrossRefPubMed

25.

Tesfaye D, Ghanem N, Carter F, Fair T, Sirard MA, Hoelker M, et al. Gene expression profile of cumulus cells derived from cumulus-oocyte complexes matured either in vivo or in vitro. Reprod Fertil Dev. 2009;21(3):451–61.CrossRefPubMed

26.

Li Q, Jimenez-Krassel F, Ireland JJ, Smith GW. Gene expression profiling of bovine preovulatory follicles: gonadotropin surge and prostanoid-dependent up-regulation of genes potentially linked to the ovulatory process. Reproduction. 2009;137(2):297–307.CrossRefPubMed

27.

Filion F, Bouchard N, Goff AK, Lussier JG, Sirois J. Molecular cloning and induction of bovine prostaglandin E synthase by gonadotropins in ovarian follicles prior to ovulation in vivo. J Biol Chem. 2001;276(36):34323–30.CrossRefPubMed

28.

Bedard J, Brule S, Price CA, Silversides DW, Lussier JG. Serine protease inhibitor-E2 (SERPINE2) is differentially expressed in granulosa cells of dominant follicle in cattle. Mol Reprod Dev. 2003;64(2):152–65.CrossRefPubMed

29.

Sambrook JF, Russell DW. Molecular cloning. A laboratory manual. vol. 3, 3rd ed. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 2001. p. 2100.

30.

Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–54.CrossRefPubMed

31.

Liu X, Zhou R, Zhang Q, Zhang Y, Shao G, Jin Y, et al. Identification and characterization of LAPTM4B encoded by a human hepatocellular carcinoma-associated novel gene. Beijing da xue xue bao Yi xue ban = Journal of Peking University Health sciences. 2003;35(4):340–7.PubMed

32.

Dikic I, Wakatsuki S, Walters KJ. Ubiquitin-binding domains - from structures to functions. Nat Rev Mol Cell Biol. 2009;10(10):659–71.CrossRefPubMed

33.

Hogue DL, Ellison MJ, Vickers M, Cass CE. Functional complementation of a membrane transport deficiency in Saccharomyces cerevisiae by recombinant ND4 fusion protein. Biochem Biophys Res Commun. 1997;238(3):811–6.CrossRefPubMed

34.

Devnath S, Inoue K. An insight to pituitary folliculo-stellate cells. J Neuroendocrinol. 2008;20(6):687–91.CrossRefPubMed

35.

Hogue DL, Kerby L, Ling V. A mammalian lysosomal membrane protein confers multidrug resistance upon expression in Saccharomyces cerevisiae. J Biol Chem. 1999;274(18):12877–82.CrossRefPubMed

36.

Li L, Wei XH, Pan YP, Li HC, Yang H, He QH, et al. LAPTM4B: a novel cancer-associated gene motivates multidrug resistance through efflux and activating PI3K/AKT signaling. Oncogene. 2010;29(43):5785–95.CrossRefPubMed

37.

Li Y, Zou L, Li Q, Haibe-Kains B, Tian R, Li Y, et al. Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer. Nat Med. 2010;16(2):214–8.CrossRefPubMedCentralPubMed

Title: Differential expression of lysosome-associated protein transmembrane-4 beta (LAPTM4B) in granulosa cells of ovarian follicles and in other bovine tissues
Authors: Kalidou Ndiaye
Paul D Carrière
Jean Sirois
David W Silversides
Jacques G Lussier
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Journal of Ovarian Research / Issue 1/2015
Electronic ISSN: 1757-2215
DOI: https://doi.org/10.1186/s13048-015-0148-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Differential expression of lysosome-associated protein transmembrane-4 beta (LAPTM4B) in granulosa cells of ovarian follicles and in other bovine tissues

Abstract

Background

Methods and results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods and results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2015

Comparative analysis of Rb1, P16 and ER as diagnostic, prognostic and potential targets for therapeutic agents in ovarian epithelial tumors: an immunohistochemical study of 130 ovarian carcinomas

Expression of the beta-2 adrenergic receptor (ADRB-2) in human and monkey ovarian follicles: a marker of growing follicles?

Corifollitropin alfa compared to daily FSH in controlled ovarian stimulation for in vitro fertilization: a meta-analysis

Use of aromatase inhibitors in practice of gynecology

The correlation of aromatase activity and obesity in women with or without polycystic ovary syndrome

Beclin-1 expression is retained in high-grade serous ovarian cancer yet is not essential for autophagy induction in vitro