Collagenα3(IV)chains are one of the major constituent components of the basement membrane in the mammalian testis.Studies have shown that biologically active fragments,such as noncollagenase domain(NC1)-peptide,can b...Collagenα3(IV)chains are one of the major constituent components of the basement membrane in the mammalian testis.Studies have shown that biologically active fragments,such as noncollagenase domain(NC1)-peptide,can be released from the C-terminal region of collagenα3(IV)chains,possibly through the proteolytic action of metalloproteinase 9(MMP9).NC1-peptide was shown to promote blood-testis barrier(BTB)remodeling and fully developed spermatid(e.g.,sperm)release from the seminiferous epithelium because this bioactive peptide was capable of perturbing the organization of both actin-and microtubule(MT)-based cytoskeletons at the Sertoli cell-cell and also Sertoli-spermatid interface,the ultrastructure known as the basal ectoplasmic specialization(ES)and apical ES,respectively.More importantly,recent studies have shown that this NC1-peptide-induced effects on cytoskeletal organization in the testis are mediated through an activation of mammalian target of rapamycin complex 1/ribosomal protein S6/transforming retrovirus Akt1/2 protein(mTORC1/rpS6/Akt1/2)signaling cascade,involving an activation of cell division control protein 42 homolog(Cdc42)GTPase,but not Ras homolog family member A GTPase(RhoA),and the participation of end-binding protein 1(EB1),a microtubule plus(+)end tracking protein(+TIP),downstream.Herein,we critically evaluate these findings,providing a critical discussion by which the basement membrane modulates spermatogenesis through one of its locally generated regulatory peptides in the testis.展开更多
基金This work was supported in part by grants from the National Institutes of Health(NICHD,R01 HD056034 to CYC)the National Natural Science Foundation of China(NSFCNo.81730042 to RSG).
文摘Collagenα3(IV)chains are one of the major constituent components of the basement membrane in the mammalian testis.Studies have shown that biologically active fragments,such as noncollagenase domain(NC1)-peptide,can be released from the C-terminal region of collagenα3(IV)chains,possibly through the proteolytic action of metalloproteinase 9(MMP9).NC1-peptide was shown to promote blood-testis barrier(BTB)remodeling and fully developed spermatid(e.g.,sperm)release from the seminiferous epithelium because this bioactive peptide was capable of perturbing the organization of both actin-and microtubule(MT)-based cytoskeletons at the Sertoli cell-cell and also Sertoli-spermatid interface,the ultrastructure known as the basal ectoplasmic specialization(ES)and apical ES,respectively.More importantly,recent studies have shown that this NC1-peptide-induced effects on cytoskeletal organization in the testis are mediated through an activation of mammalian target of rapamycin complex 1/ribosomal protein S6/transforming retrovirus Akt1/2 protein(mTORC1/rpS6/Akt1/2)signaling cascade,involving an activation of cell division control protein 42 homolog(Cdc42)GTPase,but not Ras homolog family member A GTPase(RhoA),and the participation of end-binding protein 1(EB1),a microtubule plus(+)end tracking protein(+TIP),downstream.Herein,we critically evaluate these findings,providing a critical discussion by which the basement membrane modulates spermatogenesis through one of its locally generated regulatory peptides in the testis.
