Microtubule-binding proteins (MAPs) mainly include the microtubule positive-terminal binding protein (+TIPs) and the negative-terminal binding protein (+TIPs). These proteins regulate microtubule dynamics and mediate the involvement of microtubules in a variety of cellular biological processes. At present, a variety of + TIPs have been found, whose core members are the EBs protein family. EBs can autonomously bind to the positive end of microtubules, regulate the dynamic changes of microtubules, and can recruit many other + TIPs to the positive end of microtubules, but it is unclear how EBs are regulated. Nowadays, there is still a limited understanding of -TIPs in the studies. The CAMSAPs family of proteins, as a new class of TIPs, binds to the negative end of a dynamically growing microtubule and stabilizes the negative end of the microtubule.
Recent studies on the relationship between CAMSAPs and EB1 have found that CAMSAP2 has the most significant effect on the positive localization of EB1 in microtubules. CAMSAPs bind to EB1 through the C-terminal domain, while the EB1 linker region inhibits the binding of EB1-specific domains to CAMSAPs. The results show that CAMSAP2-EB1 interaction can be independent of microtubules in the cytoplasm, and the intracellular protein content of CAMSAP2 affects the length of EB1 at the positive end of microtubules. In contrast, EB1 can also help CAMSAP2 stabilize in the microtubule negative end. With live cell imaging, it was observed that EB1 comets at the positive end of the microtubules could target the CAMSAP2 site for transient collisions with CAMSAP2, and knockdown of CAMSAP2 caused the change of the direction of EB1 movement. This implies that non-centrosome microtubules are likely to be end-to-end connected with other microtubules to participate in intracellular functions in this way , providing continuous orbit for the transport of matter over long distances. Further validation of this hypothesis by autophagy demonstrated that CAMSAP2 was able to assist the reverse transport of autophagic bodies by interacting with EB1. Autophagic small membrane protein LC3 is able to bind CAMSAP2 and EB1. These results suggest that the "bridges" of EB1 comets targeting CAMSAP2 in a transient collision construct are likely to facilitate autophagy turnover. Using live cell imaging experiments, it was found that the contact frequency of EB1 with LC3 decreased after CASMAP2 knockdown, confirming that the "EB1-CAMSAP2 bridge" helps reverse transport of autophagosomes. This study revealed the relationship between CAMSAP2 and EB1 and the function of both in intracellular. It is important to understand the relationship between the positive and negative terminal tubulin of microtubules and their role in the cell.