Differential Expression of Lysosome-associated Protein Transmembrane-4 Beta (LAPTM4B) in Granulosa Cells of Ovarian Follicles and in Other Bovine Tissues

Overview

Journal J Ovarian Res

Publisher Biomed Central

Specialties Gynecology & Obstetrics
Reproductive Medicine

Date 2015 Apr 18

PMID 25881887

Citations 5

Authors

Kalidou Ndiaye

Paul D Carriere

Jean Sirois

David W Silversides

Jacques G Lussier

Affiliations

Soon will be listed here.

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). Immunoblotting 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.

Citing Articles

Janus Kinase 3 phosphorylation and the JAK/STAT pathway are positively modulated by follicle-stimulating hormone (FSH) in bovine granulosa cells.

Zareifard A, Beaudry F, Ndiaye K BMC Mol Cell Biol. 2023; 24(1):21.

PMID: 37337185 PMC: 10280845. DOI: 10.1186/s12860-023-00482-5.

Integrative Genome-Wide DNA Methylome and Transcriptome Analysis of Ovaries from Hu Sheep with High and Low Prolific.

Yao X, Li F, Wei Z, Ei-Samahy M, Feng X, Yang F Front Cell Dev Biol. 2022; 10:820558.

PMID: 35186931 PMC: 8850840. DOI: 10.3389/fcell.2022.820558.

Two alternative methods for the retrieval of somatic cell populations from the mouse ovary.

Frost E, Ford E, Taylor G, Boeing S, Beckett E, Roman S Mol Hum Reprod. 2021; 27(6).

PMID: 33973015 PMC: 8211868. DOI: 10.1093/molehr/gaab033.

Identification of Lysosome-Associated Protein Transmembrane-4 as a Novel Therapeutic Target for Osteosarcoma Treatment.

Wang Z, Guo M, Ren J, Li G, Sun X Orthop Surg. 2020; 12(4):1253-1260.

PMID: 32558212 PMC: 7454209. DOI: 10.1111/os.12692.

Gonadotropin regulation of ankyrin-repeat and SOCS-box protein 9 (ASB9) in ovarian follicles and identification of binding partners.

Benoit G, Warma A, Lussier J, Ndiaye K PLoS One. 2019; 14(2):e0212571.

PMID: 30811458 PMC: 6392328. DOI: 10.1371/journal.pone.0212571.

References

Liu X, Zhou R, Zhang Q, Zhang Y, Shao G, Jin Y . [Identification and characterization of LAPTM4B encoded by a human hepatocellular carcinoma-associated novel gene]. Beijing Da Xue Xue Bao Yi Xue Ban. 2003; 35(4):340-7. View

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. DOI: 10.1074/jbc.M010562200. View

Liu J, Zhou R, Zhang N, Rui J, Jin C . Biological function of a novel gene overexpressed in human hepatocellular carcinoma. Chin Med J (Engl). 2002; 113(10):881-5. View

Hogue D, Ellison M, Vickers M, Cass C . Functional complementation of a membrane transport deficiency in Saccharomyces cerevisiae by recombinant ND4 fusion protein. Biochem Biophys Res Commun. 1997; 238(3):811-6. DOI: 10.1006/bbrc.1997.7400. View

Gough N, Zweifel M, Martinez-Augustin O, Aguilar R, Bonifacino J, Fambrough D . 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. DOI: 10.1242/jcs.112.23.4257. View

Ndiaye K, Fayad T, Silversides D, Sirois J, Lussier J . 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. DOI: 10.1095/biolreprod.104.038026. View

Liu X, Zhou R, Zhang Q, Zhang Y, Jin Y, Lin M . 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. PMC: 4572753. DOI: 10.3748/wjg.v10.i11.1555. View

Bedard J, Brule S, Price C, Silversides D, Lussier J . Serine protease inhibitor-E2 (SERPINE2) is differentially expressed in granulosa cells of dominant follicle in cattle. Mol Reprod Dev. 2002; 64(2):152-65. DOI: 10.1002/mrd.10239. View

Milvae R, Hinckley S, Carlson J . Luteotropic and luteolytic mechanisms in the bovine corpus luteum. Theriogenology. 1996; 45(7):1327-49. DOI: 10.1016/0093-691x(96)00100-8. View

10.

Li Y, Zhang Q, Tian R, Wang Q, Zhao J, Iglehart J . Lysosomal transmembrane protein LAPTM4B promotes autophagy and tolerance to metabolic stress in cancer cells. Cancer Res. 2011; 71(24):7481-9. PMC: 3261660. DOI: 10.1158/0008-5472.CAN-11-0940. View

11.

Adra C, Zhu S, Ko J, Guillemot J, Cuervo A, Kobayashi H . LAPTM5: a novel lysosomal-associated multispanning membrane protein preferentially expressed in hematopoietic cells. Genomics. 1996; 35(2):328-37. DOI: 10.1006/geno.1996.0364. View

12.

Rosenfeld C, Wagner J, Roberts R, Lubahn D . Intraovarian actions of oestrogen. Reproduction. 2001; 122(2):215-26. DOI: 10.1530/rep.0.1220215. View

13.

Webb R, Nicholas B, Gong J, Campbell B, Gutierrez C, Garverick H . Mechanisms regulating follicular development and selection of the dominant follicle. Reprod Suppl. 2003; 61:71-90. View

14.

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. 2003; 35(4):348-52. View

15.

Marks M, Woodruff L, Ohno H, Bonifacino J . Protein targeting by tyrosine- and di-leucine-based signals: evidence for distinct saturable components. J Cell Biol. 1996; 135(2):341-54. PMC: 2121048. DOI: 10.1083/jcb.135.2.341. View

16.

Mihm M, Bleach E . Endocrine regulation of ovarian antral follicle development in cattle. Anim Reprod Sci. 2003; 78(3-4):217-37. DOI: 10.1016/s0378-4320(03)00092-7. View

17.

Li L, Wei X, Pan Y, Li H, Yang H, He Q . LAPTM4B: a novel cancer-associated gene motivates multidrug resistance through efflux and activating PI3K/AKT signaling. Oncogene. 2010; 29(43):5785-95. DOI: 10.1038/onc.2010.303. View

18.

Kasper G, Vogel A, Klaman I, Grone J, Petersen I, Weber B . 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. DOI: 10.1016/j.canlet.2004.10.004. View

19.

Morris D, Musat M, Czirjak S, Hanzely Z, Lillington D, Korbonits M . Differential gene expression in pituitary adenomas by oligonucleotide array analysis. Eur J Endocrinol. 2005; 153(1):143-51. DOI: 10.1530/eje.1.01937. View

20.

Eppig J, Wigglesworth K, Pendola F . The mammalian oocyte orchestrates the rate of ovarian follicular development. Proc Natl Acad Sci U S A. 2002; 99(5):2890-4. PMC: 122443. DOI: 10.1073/pnas.052658699. View