The CLIP-170 N-terminal domain binds directly to both F-actin and microtubules in a mutually exclusive manner

• DOI: 10.1016/j.jbc.2022.101820
• Publication Date: 2022-03-10T07:10:46Z
• Authors: Yueh-Fu O. Wu; Rachel A. Miller; Emily O. Alberico; Yaobing A.P. Huang; Annamarie T. Bryant; Nora T. Nelson; Erin M. Jonasson; Holly V. Goodson
• Keywords: Formins; MDia1; Actin-binding protein; Actin remodeling; IQGAP1; Cell Cortex; Treadmilling

The cooperation between the actin and microtubule (MT) cytoskeletons is important for cellular processes such as cell migration muscle development. However, a full understanding of how this occurs has yet to be sufficiently developed. MT plus-end tracking protein CLIP-170 been implicated in actin-MT coordination by associating with actin-binding signaling IQGAP1 promoting polymerization through binding formins. Thus far, interactions were assumed indirect. Here, we demonstrate using high-speed cosedimentation assays that can bind filamentous (F-actin) directly. We found affinity relatively weak but strong enough significant actin-rich cortex, where concentrations extremely high. Using fragments mutants, show direct CLIP-170-F-actin interaction independent FEED domain, region mediates formin-dependent polymerization, F-actin-binding overlaps MT-binding region. Consistent these observations, vitro competition indicate CLIP-170-MT are mutually exclusive. Taken together, observations lead us speculate may function reduce stability MTs regions cell, previously proposed end-binding 1.