A Role for CLASPs in the Regulation of the Major Microtubule +TIP Complex Organizers, End-Binding Proteins

Abstract

Microtubule plus-end tracking proteins (+TIPs) are a specialized group of microtubule-associated proteins (MAPs) that preferentially localize to microtubule (MT) plus-ends. This unique localization is thought to be due to +TIP recognition of a unique structural or chemical feature found only at the plus-ends of MTs, such as the GTP- tubulin cap. End-binding proteins (EBs) are considered the master regulators of the +TIP network; however, whether EBs are regulated by other +TIP proteins is not well understood. Therefore, a study of the regulation of EB proteins by CLASPs (CLIP-associated proteins), another family of +TIPs, was undertaken.

In cells lacking CLASPs, EB binding at MTs is significantly altered: both EB1 and EB3 relocalized to the MT lattice in addition to their characteristic plus-end localization. This study reveals that CLASPs likely function during MT polymerization to support efficient GTP-hydrolysis and thus promote specific EB plus-end localization. This work establishes CLASPs as crucial determinants of proper EB localization at MTs in cells.