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Cross-talk between MT +TIPs and -TIPs Regulates Intracellular Transport
The dynamic instability of microtubule (MT) is regulated by a large number of proteins called microtubule-associated proteins (MAPs), including plus-end-tracking proteins (+TIPs) and minus-end-targeting proteins (-TIPs). Lots of +TIPs have been identified. Among them, the mammalian end-binding proteins, EBs (EB1, 2 and 3) are considered to be the core +TIPs. However, the mechanisms regulating EBs remain largely unknown. In contrast to +TIPs, only a small number of -TIPs have been identified, such as the CAMSAPs family (CAMSAP1, 2 and 3 in mammals). Recent work suggested that CAMSAPs depletion elongated EB1 length at MT plus ends, while the underlying mechanisms are unclear.
In a recent study, researchers from MENG Wenxiang group at the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, used a combination of biochemistry analysis, immunofluorescent staining and live-cell imaging to determine the relationship between CAMSAPs and EB1 and their roles in cells.
First, the researches identified that -TIPs CAMSAPs interact with +TIPs EB1, and showed that CAMSAP2 redistributes EB1 localization along MT plus ends could through cytosol interaction. Moreover, live-cell imaging showed that many EB1 comets transiently contact CAMSAP2 stretches. Furthermore, CAMSAP2 depletion induced an alteration of EB1 moving orientations, suggesting that CAMSAP2 and EB1 connect two MTs to provide continuous railways for long-range transport of cargos along MTs.
Their results demonstrate that CAMSAP2 facilitates the retrograde transport of autophagosomes via interacting with EB1. In addition, the autophagosome adaptor LC3 interacted with both CAMSAP2 and EB1, suggesting they associate at the intersection of the plus end of a MT and another minus end of noncentrosomal MT. They also found that CAMSAP2 depletion decreases the frequency of EB1-LC3 contact. These suggest that noncentrosomal MTs facilitate autophagosome transit through EB1- CAMSAP2 interaction.
This work, entitled “Noncentrosomal microtubules regulate autophagosome transport through CAMSAP2-EB1 cross-talk”, has been published on FEBS Letters (FEBS Lett 591, 2379-2393; DOI: 10.1002/1873-3468.12758) with PhD candidate WEI Jieli as first authors.
This work was supported by the National Natural Science Foundation of China, the National Basic Research Program of China, and the Key Research Program of the Chinese Academy of Sciences.
Noncentrosomal MTs regulate retrograde transport of autophagosomes through CAMSAP2-EB1 cross-talk. (Image by IGDB)
Dr. MENG Wenxiang