Katnip is needed to maintain microtubule function and lysosomal delivery to autophagosomes and phagosomes.
Katnip is needed to maintain microtubule function and lysosomal delivery to autophagosomes and phagosomes.
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DOI：
10.1091/mbc.e22-02-0063
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发表时间：
2023-03-01
影响因子：
3.3
通讯作者：
King, Jason S.
中科院分区：
文献类型：
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作者：
Starling, Georgina P.;Phillips, Ben A.;Ganesh, Sahana;King, Jason S.
溶酶体的有效传递对许多细胞功能是必不可少的，例如通过自噬降解细胞内不需要的成分，以及杀死和消化吞噬体内的细胞外微生物。利用盘状网囊阿米巴，我们发现缺乏Katnip(katanin相互作用蛋白)的细胞在溶酶体递送方面存在普遍缺陷，尽管它们正确地制造自噬小体和吞噬小体，但细胞无法消化它们。Katnip在很大程度上没有被研究，但在进化过程中高度保守。此前的研究发现，Katnip基因突变会导致动物纤毛结构的缺陷。在这里，我们展示了Katnip在维持微管功能方面发挥的更广泛的作用。我们发现，Katnip的丢失对微管的动力学或组织没有总体影响，但对内吞货物的运输和降解是重要的。值得注意的是，Katnip突变体对GFP-微管蛋白的表达高度敏感，这导致微管缠绕，后期延伸有缺陷，细胞生长缓慢。我们的发现确立了Katnip在调节微管功能方面的一般作用，而不是先前在纤毛中描述的作用。我们推测这是通过微管修复中的一个关键功能实现的，微管修复是维持内小体运输和溶酶体降解所必需的。
The efficient delivery of lysosomes is essential for many cell functions, such as the degradation of unwanted intracellular components by autophagy and the killing and digestion of extracellular microbes within phagosomes. Using the amoeba Dictyostelium discoideum, we find that cells lacking Katnip (Katanin interacting protein) have a general defect in lysosomal delivery and although they make autophagosomes and phagosomes correctly, cells are then unable to digest them. Katnip is largely unstudied yet highly conserved across evolution. Previously studies found that Katnip mutations in animals cause defects in cilia structure. Here we show that Katnip plays a more general role in maintaining microtubule function. We find that loss of Katnip has no overall effect on microtubule dynamics or organization, but is important for the transport and degradation of endocytic cargos. Strikingly, Katnip mutants become highly sensitive to GFP–tubulin expression, which leads to microtubule tangles, defective anaphase extension, and slow cell growth. Our findings establish a general role for Katnip in regulating microtubule function, beyond the roles previously described in cilia. We speculate this is via a key function in microtubule repair, needed to maintain endosomal trafficking and lysosomal degradation.