Katnip is required to maintain microtubule function and lysosomal delivery to autophagosomes and phagosomes

Abstract

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 lysosome delivery and whilst able to make autophagosomes and phagosomes correctly are then unable to digest them. Katnip is largely unstudied yet highly conserved across evolution. Previously studies found Katnip mutations in animals cause defects in cilia structure. Here we show that Katnip plays a general role in maintaining microtubule function. We find that loss of Katnip has no overall effect on microtubule dynamics or organisation, 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 growth. Our findings establish a conserved role for Katnip in the function of all microtubules, not just cilia as previously reported. We speculate this is via a key function in microtubule repair, required to maintain endosomal trafficking and lysosomal degradation.