- Grimaldi AD, Maki T, Fitton BP, Roth D, Yampolsky D, Davidson MW, Svitkina T, Straube A, Hayashi I, Kaverina I. CLASPs are required for proper microtubule localization of end-binding proteins. Developmental cell. 2014 Aug 11;30(3). 343-52. PMID: 25117684 [PubMed]. PMCID: PMC4133696. NIHMSID: NIHMS611375.
Microtubule (MT) plus-end tracking proteins (+TIPs) preferentially localize to MT plus ends. End-binding proteins (EBs) are master regulators of the +TIP complex; however, it is unknown whether EBs are regulated by other +TIPs. Here, we show that cytoplasmic linker-associated proteins (CLASPs) modulate EB localization at MTs. In CLASP-depleted cells, EBs localized along the MT lattice in addition to plus ends. The MT-binding region of CLASP was sufficient for restoring normal EB localization, whereas neither EB-CLASP interactions nor EB tail-binding proteins are involved. In vitro assays revealed that CLASP directly functions to remove EB from MTs. Importantly, this effect occurs specifically during MT polymerization, but not at preformed MTs. Increased GTP-tubulin content within MTs in CLASP-depleted cells suggests that CLASPs facilitate GTP hydrolysis to reduce EB lattice binding. Together, these findings suggest that CLASPs influence the MT lattice itself to regulate EB and determine exclusive plus-end localization of EBs in cells.