Journal article
Spatiotemporal coordination of actin regulators generates invasive protrusions in cell-cell fusion
Nature cell biology, Vol.26(11), pp.1860-1877
11/2024
DOI: 10.1038/s41556-024-01541-5
PMCID: PMC12164543
PMID: 39487253
Abstract
Invasive membrane protrusions play a central role in a variety of cellular processes. Unlike filopodia, invasive protrusions are mechanically stiff and propelled by branched actin polymerization. However, how branched actin filaments are organized to create finger-like invasive protrusions is unclear. Here, by examining the mammalian fusogenic synapse, where invasive protrusions are generated to promote cell membrane juxtaposition and fusion, we have uncovered the mechanism underlying invasive protrusion formation. We show that two nucleation-promoting factors for the Arp2/3 complex, WAVE and N-WASP, exhibit different localization patterns in the protrusions. Whereas WAVE is closely associated with the plasma membrane at the leading edge of the protrusive structures, N-WASP is enriched with WIP along the actin bundles in the shafts of the protrusions. During protrusion initiation and growth, the Arp2/3 complex nucleates branched actin filaments to generate low-density actin clouds in which the large GTPase dynamin organizes the new branched actin filaments into bundles, followed by actin-bundle stabilization by WIP, the latter functioning as an actin-bundling protein. Disruption of any of these components results in defective protrusions and failed myoblast fusion in cultured cells and mouse embryos. Together, our study has revealed the intricate spatiotemporal coordination between two nucleation-promoting factors and two actin-bundling proteins in building invasive protrusions at the mammalian fusogenic synapse and has general implications in understanding invasive protrusion formation in cellular processes beyond cell-cell fusion.
Details
- Title: Subtitle
- Spatiotemporal coordination of actin regulators generates invasive protrusions in cell-cell fusion
- Creators
- Yue Lu - The University of Texas Southwestern Medical CenterTezin Walji - The University of Texas Southwestern Medical CenterBenjamin Ravaux - The University of Texas Southwestern Medical CenterPratima Pandey - The University of Texas Southwestern Medical CenterChangsong Yang - University of PennsylvaniaBing Li - The University of Texas Southwestern Medical CenterDelgermaa Luvsanjav - Johns Hopkins UniversityKevin H Lam - The University of Texas at DallasRuihui Zhang - The University of Texas Southwestern Medical CenterZhou Luo - The University of Texas Southwestern Medical CenterChuanli Zhou - The University of Texas Southwestern Medical CenterChrista W Habela - Johns Hopkins UniversityScott B Snapper - Boston Children's HospitalRong Li - Johns Hopkins UniversityDavid J Goldhamer - University of ConnecticutDavid W Schmidtke - The University of Texas at DallasDuojia Pan - The University of Texas Southwestern Medical CenterTatyana M Svitkina - University of PennsylvaniaElizabeth H Chen - The University of Texas Southwestern Medical Center
- Resource Type
- Journal article
- Publication Details
- Nature cell biology, Vol.26(11), pp.1860-1877
- DOI
- 10.1038/s41556-024-01541-5
- PMID
- 39487253
- PMCID
- PMC12164543
- NLM abbreviation
- Nat Cell Biol
- ISSN
- 1465-7392
- eISSN
- 1476-4679
- Grant note
- R35GM140832 / U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01AR052777 / U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) R35 GM136316 / NIGMS NIH HHS R01 AR052777 / NIAMS NIH HHS R35GM136316 / U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01 AR075005 / NIAMS NIH HHS R35 GM140832 / NIGMS NIH HHS
- Language
- English
- Date published
- 11/2024
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9985150205702771
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