Nlp promotes autophagy through facilitating the interaction of Rab7 and FYCO1

Wenchang Xiao,Zhangfu Li,Danna Yeerken,Jia Li,Liying Ma,Ming Fu,Weimin Zhang,Lanfang Jiang,Dan Li,Yongmei Song,Qimin Zhan

doi:10.1038/s41392-021-00543-1

Abstract

Autophagy is the main degradation pathway to eliminate long-lived and aggregated proteins, aged or malfunctioning organelles, which is essential for the intracellular homeostasis and prevention of malignant transformation. Although the processes of autophagosome biogenesis have been well illuminated, the mechanism of autophagosome transport remains largely unclear. In this study, we demonstrated that the ninein-like protein (Nlp), a well-characterized centrosomal associated protein, was able to modulate autophagosome transport and facilitate autophagy. During autophagy, Nlp colocalized with autophagosomes and physically interacted with autophagosome marker LC3, autophagosome sorting protein Rab7 and its downstream effector FYCO1. Interestingly, Nlp enhanced the interaction between Rab7 and FYCO1, thus accelerated autophagic flux and the formation of autophagolysosomes. Furthermore, compared to the wild-type mice, NLP deficient mice treated with chemical agent DMBA were prone to increased incidence of hepatomegaly and liver cancer, which were tight associated with the hepatic autophagic defect. Taken together, our findings provide a new insight for the first time that the well-known centrosomal protein Nlp is also a new regulator of autophagy, which promotes the interaction of Rab7 and FYCO1 and facilitates the formation of autophagolysosome.

Highlights

Autophagy is a catabolic process by which eukaryotic cells portions of their own cytoplasm,[1] such as protein aggregates, aged or even malfunctioning organelles.[2]
We replaced the complete growth medium DMEM with Hank’s balanced salt solution (HBSS) for 4 h, which is usually used for inducing autophagy
In the HBSS condition, the puncta of ninein-like protein (Nlp) were more apparent (Fig. 1a). These observations suggested that in autophagy inducing cells, Nlp was more likely to function as puncta in the cytosol, similar to some autophagosome marker and autophagy-related proteins (ATG)

Summary

Introduction

Autophagy is a catabolic process by which eukaryotic cells portions of their own cytoplasm,[1] such as protein aggregates, aged or even malfunctioning organelles.[2]. Autophagy is commonly described as the processes during which vesicles containing cytosolic cargo, called autophagosomes, are transported to lysosomes and fuse, to form the so-called autophagolysosomes,[4] in which the degradation happens. The autophagosome is formed once the phagophore is sealed to be a closed, double-membrane vesicle.[5] Genetic screens in yeast have identified a group of autophagy-related proteins (ATG), which are mostly involved in the formation of autophagosomes.[6] Once an autophagosome is formed, it is transport to the cortex area in cytosol, there autophagosome is fused with lysosome to form an autophagolysosome.[7] Autophagolysosome is considered to be the final modality of vesicles containing cellular waste cargo.[8] The processes of the formation and degradation of autophagosome are well elucidated. The transportation of autophagosome in the cytosol remains largely unclear

Methods

Results

Conclusion