Role of NBR1-regulated selective autophagy in growth and development of filamentous fungi

自噬字面意思是“自食”，描述了动物溶酶体或植物和真菌液泡内降解和再循环的进化保守的真核生物过程。有两种类型的自噬被描述：非选择性和选择性自噬。非选择性自噬是细胞质和细胞器随机吞噬到双膜囊泡中，自噬体将货物运送到液泡中进行降解。在选择性自噬中，特定的货物如细胞器、蛋白质聚集体或酶被货物受体识别并包裹在自噬体中。对于有性繁殖，丝状真菌产生三维子实体，在那里产生性子囊孢子。同源子囊菌大孢子Sordaria macrospora是研究多细胞子实体发育的优良真菌模式生物。在我们之前的研究中，我们已经表明，非选择性自噬是大孢子葡萄球菌维持丝状生长和多细胞发育的高能量水平所必需的和组成活性的过程。然而，选择性自噬在多细胞结构（如丝状子囊菌的子实体）发育中的作用尚未得到详细研究。我们能够证明BRCA1的哺乳动物选择性货物受体邻居（NBR1） Sm的同源物NBR1在大孢子葡萄球菌中作为腐食（过氧化物酶体的选择性降解）受体。我们建立了SmNBR1-BioID方法，并证实BioID方法适用于鉴定新的假定的连接SmNBR1与不同底物的接头蛋白。我们旨在了解smnbr1介导的选择性自噬，特别是大孢子S. macrospora的自噬的机制和调控，并试图为选择性自噬在丝状真菌和高等真核生物发育中的作用提供见解。

Autophagy literally implying “self-eating”, describes an evolutionarily conserved eukaryotic process of degradation and recycling within lysosomes in animals or vacuoles in plants and fungi. Two types of autophagy have been described: non-selective and selective autophagy. Non-selective autophagy is the random engulfment of cytoplasm and organelles into double-membrane vesicles, the autophagosomes, which deliver the cargo to the vacuole for degradation. In selective autophagy, specific cargos such as organelles, protein aggregates or enzymes are recognized by cargo receptors and enwrapped into autophagosomes. For sexual propagation, filamentous fungi produce three-dimensional fruiting bodies, where the sexual ascospores are generated. The homothallic (self-fertile) ascomycete Sordaria macrospora is an excellent fungal model organism to study multicellular fruiting-body development. In our previous studies, we had shown that non-selective autophagy is an essential and constitutively active process required to maintain high energy levels for filamentous growth and multicellular development in S. macrospora. However, the role of selective autophagy in the development of multicellular structures, such as fruiting bodies in filamentous ascomycetes has not yet been investigated in detail. We were able to demonstrate that a homolog of the mammalian selective cargo receptor Neighbor of BRCA1 (NBR1) Sm NBR1 acts as a receptor for pexophagy (selective degradation of peroxisomes) in S. macrospora. We established the SmNBR1-BioID method and confirmed that the BioID method is applicable in identifying new putative adaptor proteins linking SmNBR1 with diverse substrates. We aim to understand the mechanism and regulation of SmNBR1-mediated selective autophagy and in particular pexophagy in S. macrospora, and intend to provide insights into the role of selective autophagy in the development of filamentous fungi and higher eukaryotes.