Latrunculins—novel marine macrolides that disrupt microfilament organization and affect cell growth: I. Comparison with cytochalasin D
Abstract
The latrunculins are architecturally novel marine compounds isolated from the Red Sea sponge Latrunculia magnifica. In vivo, they alter cell shape, disrupt microfilament organization, and inhibit the microfilament‐mediated processes of fertilization and early development. In vitro, latrunculin A was recently found to affect the polymerization of pure actin in a manner consistent with the formation of a 1:1 molar complex with G‐actin. These in vitro effects as well as previous indications that the latrunculins are more potent than the cytochalasins suggest differences in the in vivo mode of action of the two clases of drugs. To elucidate these differences we have compared the short‐ and long‐term effects of latrunculins on cell shape and actin organization to those of cytochalasin D. Exposure of hamster fibroblast NIL8 cells for 1–3 hr to latrunculin A, latrunculin B, and cytochalasin D causes concentration‐dependent changes in cell shape and actin organization. However, the latrunculin‐induced changes were strikingly different from those induced by cytochalasin D. Furthermore, while initial effects were manifest with both latrunculin A and cytochalasin D already at concentrations of about 0.03 μg/ml, latrunculin A caused complete rounding up of all cells at 0.2 μg/ml, whereas with cytochalasin D maximum contraction was reached at concentrations 10–20 times higher. The short‐term effects of latrunculin B were similar to those of latrunculin A although latrunculin B was slightly less potent. All three drugs inhibited cytokinesis in synchronized cells, but their long‐term effects were markedly different. NIL8 cells treated with latrunculin A maintained their altered state for extended periods. In contrast, the effects of cytochalasin D progressed with time in culture, and the latrunculin B‐induced changes were transient in the continued presence of the drug. These transient effects were found to be due to a gradual inactivation of latrunculin B by serum and were used to compare recovery patterns of cell shape and actin organization in two different cell lines. This comparison showed that the transient effects of latrunculin B were fully reversible for the NIL8 cells and not for the mouse neuroblastoma N1E‐115 cells.
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Latrunculins bind to G-actin in a 1:1 molar complex, thereby limiting the availability of actin monomers for polymerizing at either barbed or pointed ends of actin filaments.
“Latrunculins bind to G-actin in a 1:1 molar complex, thereby limiting the availability of actin monomers for polymerizing at either barbed or pointed ends of actin filaments (4).”
From Dynamic actin filaments are required for stable long-term potentiation (LTP) in area CA1 of the hippocampus (2000) · cites this paper as [4]
Low concentrations of AAIs (0.01-1 μM) are similar to those shown previously to alter actin filament organization in cultured cells, prevent lamellipodial ruffling in fibroblasts, inhibit motility and retrograde flow in neuronal growth cones, and arrest dendritic spine motility in hippocampal neurons.
“The concentrations of latrunculin A and cytochalasins used here (0.01–1 μM) are similar to those that have been shown previously to alter actin filament organization in cultured cells, prevent lamellipodial ruffling in fibroblasts, inhibit motility and retrograde flow in neuronal growth cones, and arrest dendritic spine motility in hippocampal neurons (3, 4, 7, 10).”
From Dynamic actin filaments are required for stable long-term potentiation (LTP) in area CA1 of the hippocampus (2000) · cites this paper as [4]
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- Authors
- Spector, I., Shochet, N. R., Blasberger, D., & Kashman, Y.
- Affiliations
- State University of New York (US)
- Tel Aviv University (IL)
- Corresponding author
- Spector, Ilan
- Venue
- Cell Motility
- Publisher
- Wiley
- Published
- 1989-01
- Volume
- 13
- Issue
- 3
- Pages
- 127-144
- ISSN
- 0886-1544 (ISSN-L)
- OpenAlex
- W2012652910
- Cited by
- 580
- References
- 42
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 9 · 2023: 5 · 2022: 6 · 2021: 11 · 2020: 13 · 2019: 12 · 2018: 15 · 2017: 9 · 2016: 14 · 2015: 20 · 2014: 27 · 2013: 12 · 2012: 16
- FWCI
- 0.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell Motility and the Cytoskeleton (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (GM 32776)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Marine Sponges and Natural Products
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- latrunculin, latrunculin A, latrunculin B, cytochalasin D, marine macrolides, actin polymerization, microfilament organization, cell shape, cytokinesis inhibition, actin cytoskeleton, reversible drug effects, N1E-115 neuroblastoma cells
- MeSH terms
- Animals, Cell Division, Cells, Cultured, Cytochalasins, Cytoskeleton, Cricetinae, Actin Cytoskeleton, Microscopy, Fluorescence, Thiazoles, Time Factors, Cytochalasin D, Bridged Bicyclo Compounds, Heterocyclic, Mice, Thiazolidines
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