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

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

The Journal of biological chemistry 2022 May

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The cooperation between the actin and microtubule (MT) cytoskeletons is important for cellular processes such as cell migration and muscle cell development. However, a full understanding of how this cooperation occurs has yet to be sufficiently developed. The MT plus-end tracking protein CLIP-170 has been implicated in this actin-MT coordination by associating with the actin-binding signaling protein IQGAP1 and by promoting actin polymerization through binding with formins. Thus far, the interactions of CLIP-170 with actin were assumed to be indirect. Here, we demonstrate using high-speed cosedimentation assays that CLIP-170 can bind to filamentous actin (F-actin) directly. We found that the affinity of this binding is relatively weak but strong enough to be significant in the actin-rich cortex, where actin concentrations can be extremely high. Using CLIP-170 fragments and mutants, we show that the direct CLIP-170-F-actin interaction is independent of the FEED domain, the region that mediates formin-dependent actin polymerization, and that the CLIP-170 F-actin-binding region overlaps with the MT-binding region. Consistent with these observations, in vitro competition assays indicate that CLIP-170-F-actin and CLIP-170-MT interactions are mutually exclusive. Taken together, these observations lead us to speculate that direct CLIP-170-F-actin interactions may function to reduce the stability of MTs in actin-rich regions of the cell, as previously proposed for MT end-binding protein 1. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

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. The CLIP-170 N-terminal domain binds directly to both F-actin and microtubules in a mutually exclusive manner. The Journal of biological chemistry. 2022 May;298(5):101820