PDF(Pubmed)
Abstract：
The ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family metalloprotease MIG-17 plays a crucial role in the migration of gonadal distal tip cells (DTCs) in Caenorhabditis elegans. MIG-17 is secreted from the body wall muscle cells and localizes to the basement membranes (BMs) of various tissues including the gonadal BM where it regulates DTC migration through its catalytic activity. Missense mutations in the BM protein genes, let-2/collagen IV a2 and fbl-1/fibulin-1, have been identified as suppressors of the gonadal defects observed in mig-17 mutants. Genetic analyses indicate that LET-2 and FBL-1 act downstream of MIG-17 to regulate DTC migration. In addition to the control of DTC migration, MIG-17 also plays a role in healthspan, but not in lifespan. Here, we examined whether let-2 and fbl-1 alleles can suppress the age-related phenotypes of mig-17 mutants. let-2(k196) fully and fbl-1(k201) partly, but not let-2(k193) and fbl-1(k206), suppressed the senescence defects of mig-17. Interestingly, fbl-1(k206), but not fbl-1(k201) or let-2 alleles, exhibited an extended lifespan compared to the wild type when combined with mig-17. These results reveal allele specific interactions between let-2 or fbl-1 and mig-17 in age-related phenotypes, indicating that basement membrane physiology plays an important role in organismal aging.
摘要：
ADAMTS（一种具有血小板反应蛋白基序的整合素和金属蛋白酶）家族金属蛋白酶MIG-17在秀丽隐杆线虫的性腺远端尖端细胞（DTC）的迁移中起着至关重要的作用。MIG-17从体壁肌肉细胞分泌并定位于包括性腺BM在内的各种组织的基底膜（BM），在那里它通过其催化活性调节DTC迁移。BM蛋白基因的错义突变，let-2/胶原IVa2和fbl-1/fibulin-1已被鉴定为在mig-17突变体中观察到的性腺缺陷的抑制因子。遗传分析表明LET-2和FBL-1作用于MIG-17下游以调节DTC迁移。除了控制DTC迁移之外，MIG-17在健康方面也起作用，但不是在生命中。这里,我们检查了let-2和fbl-1等位基因是否可以抑制mig-17突变体的年龄相关表型。全部let-2(k196)和部分fbl-1(k201),但不是let-2(k193)和fbl-1(k206)，抑制了mig-17的衰老缺陷。有趣的是,fbl-1(k206),但不是fbl-1(k201)或let-2等位基因，当与mig-17组合时，与野生型相比显示出延长的寿命。这些结果揭示了年龄相关表型中let-2或fbl-1和mig-17之间的等位基因特异性相互作用，表明基底膜生理在机体衰老中起着重要作用。
