Short Linear Sequence Motif LxxPTPh Targets Diverse Proteins to Growing Microtubule Ends

Abstract

Microtubule plus-end tracking proteins (+TIPs) are involved in virtually all microtubule-based processes. End-binding (EB) proteins are considered master regulators of+TIP interaction networks, since they autonomously track growing microtubule ends and recruit a plethora of proteins to this location. Two major EB-interacting elements have been described: CAP-Gly domains and linear SxIP sequence motifs. Here, we identified LxxPTPh as a third EB-binding motif that enables major+TIPs to interact with EBs at microtubule ends. In contrast to EB-SxIP and EB-CAP-Gly, the EB-LxxPTPh binding mode does not depend on the C-terminal tail region of EB. Our study reveals that+TIPs developed additional strategies besides CAP-Gly and SxIP to target EBs at growing microtubule ends. They further provide a unique basis to discover novel+TIPs, and todissect the role of key interaction nodes and their differential regulation for hierarchical+TIP network organization and function in eukaryotic organisms.