title: Clusterin signals via ApoER2/VLDLR and induces meiosis of male germ cells.
abstract: Clusterin (CLU) is a ubiquitously expressed heterodimeric glycoprotein that is involved in a variety of functions like cell-cell interactions, apoptosis, epithelial-mesenchymal transition, carcinogenesis, and chaperone function. In the testis, CLU is strongly expressed especially in Sertoli cells but very little is known about its testicular function, regulation of secretion and most enigmatic, its receptor(s). In this study, we approached these questions with a special emphasis on the link between CLU and meiosis. In cultured seminiferous tubules, we found that secretion of CLU protein is upregulated by transforming growth factor-betas (TGF-β1-3) and observed inhibition of staurosporine-induced apoptosis by recombinant CLU. Clusterin signaling in testicular cells seems to be modulated by very low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2), because these members of the low density lipoprotein (LDL) receptor family are present in rat germ cells. Furthermore, inhibition of VLDLR/ApoER2 by a specific inhibitor abrogates CLU-mediated phosphorylation of Akt, which mediates VLDLR/ApoER2 signaling. We could also show in tubules treated with recombinant CLU a significant upregulation of several meiosis-associated proteins such as V-myb avian myeloblastosis viral oncogene homolog-like 1 (Mybl1), stimulated by retinoic acid gene 8 (Stra8), lactate dehydrogenase C (LDHC), cAMP response element-binding protein (CREB) and histone H3 (H3S10P). Collectively, our data show for the first time the involvement of CLU in upregulation of meiosis through VLDLR/ApoER2 in male germ cells.
authors.affiliation: Center of Gynecology and Obstetrics, Medical Faculty, Feulgenstr. 12, Justus-Liebig-University Giessen 35392, Giessen, Germany.
authors.forename: Muhammad Assad
authors.initials: MA
authors.lastname: Riaz
authors.affiliation: Institute of Anatomy and Cell Biology, Signaling Group, Justus-Liebig-University Giessen 35392, Giessen, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Stammler
authors.affiliation: Center of Gynecology and Obstetrics, Medical Faculty, Feulgenstr. 12, Justus-Liebig-University Giessen 35392, Giessen, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Borgers
authors.affiliation: Center of Gynecology and Obstetrics, Medical Faculty, Feulgenstr. 12, Justus-Liebig-University Giessen 35392, Giessen, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Konrad
keywords: Akt; ApoER2; Clusterin; VLDLR; male germ cells; meiosis