Collective dynamics of actin and microtubule and its crosstalk mediated by FHDC1

Chee San Tong; Maohan Su; He Sun; Xiang Le Chua; Ding Xiong; Su Guo; Ravin Raj; Nicole Wen Pei Ong; Ann Gie Lee; Yansong Miao; Min Wu

doi:10.3389/fcell.2023.1261117

Collective dynamics of actin and microtubule and its crosstalk mediated by FHDC1

Front Cell Dev Biol. 2024 Mar 19:11:1261117. doi: 10.3389/fcell.2023.1261117. eCollection 2023.

Authors

Chee San Tong^#^{1

2}, Maohan Su^#^{1

2

3}, He Sun⁴, Xiang Le Chua^{1

2}, Ding Xiong⁵, Su Guo², Ravin Raj⁶, Nicole Wen Pei Ong⁶, Ann Gie Lee⁶, Yansong Miao⁴, Min Wu^{1

2

3}

Affiliations

¹ Department of Cell Biology, Yale University School of Medicine, New Haven, CT, United States.
² Department of Biological Sciences, Centre for Bioimaging Sciences, Singapore, Singapore.
³ Mechanobiology Institute, National University of Singapore, Singapore, Singapore.
⁴ School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
⁵ State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
⁶ Special Programme in Science, National University of Singapore, Singapore, Singapore.

^# Contributed equally.

Abstract

The coordination between actin and microtubule network is crucial, yet this remains a challenging problem to dissect and our understanding of the underlying mechanisms remains limited. In this study, we used travelling waves in the cell cortex to characterize the collective dynamics of cytoskeletal networks. Our findings show that Cdc42 and F-BAR-dependent actin waves in mast cells are mainly driven by formin-mediated actin polymerization, with the microtubule-binding formin FH2 domain-containing protein 1 (FHDC1) as an early regulator. Knocking down FHDC1 inhibits actin wave formation, and this inhibition require FHDC1's interaction with both microtubule and actin. The phase of microtubule depolymerization coincides with the nucleation of actin waves and microtubule stabilization inhibit actin waves, leading us to propose that microtubule shrinking and the concurrent release of FHDC1 locally regulate actin nucleation. Lastly, we show that FHDC1 is crucial for multiple cellular processes such as cell division and migration. Our data provided molecular insights into the nucleation mechanisms of actin waves and uncover an antagonistic interplay between microtubule and actin polymerization in their collective dynamics.

Keywords: FHDC1; actin waves; cell cortex; formins; microtubule.

Associated data

Dryad/10.5061/dryad.866t1g1wj

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work is supported by the National Research Foundation (NRF) Singapore under its NRF Fellowship Program (MW, NRF Award No. NRF-NRFF2011-09), Ministry of Education Academic Research Fund Tier 2 (MW, 2015-T2-1-122), Yale University startup grant (MW) and National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM151344 (MW). CT was supported by a NUS Research Scholarship. MS was supported by a MBI Scholarship. HS was supported by MOE Tier 2 (MOE2016-T2-1-005S) to YM.