Published 18 January 2005. doi:10.1083/jcb1682iti4
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 168, Number 2, 173-173
Actin-myosin tears it up
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Actin-myosin pulls apart the nuclear envelope during apoptosis.
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Caspase cleavage of nuclear lamin proteins was thought to be sufficient to cause disintegration of the nucleus during apoptosis. Now, Croft et al. (page 245) show that the actin-myosin cytoskeleton generates a pulling force required to tear apart the structure.When studying the role of actin and myosin in plasma membrane blebbing and cell contraction during apoptosis, the team noticed that if they inhibited ROCK I, a kinase that increases actin contractility and is activated by caspase cleavage, DNA was efficiently fragmented but did not end up in the expected biochemical fractions. The team hypothesized that ROCK I and the actin cytoskeleton might be involved in apoptotic nuclear breakdown.
In the current study, Croft et al. found that after blocking ROCK I activity and thus myosin light chain (MLC) phosphorylation, the nuclear envelope remained intact. Thus, the actin-myosin cytoskeleton is required for apoptotic nuclear breakdown, even though it is microtubules that do the similar job of nuclear envelope breakdown during mitosis. Furthermore, transfecting cells with a mutant form of MLC that prevents actin bundling and contraction prevented both plasma membrane blebbing—as expected from previous results—and nuclear envelope breakdown. The team also found that myosin ATPase activity, which catalyzes shortening of actin filaments, was required for nuclear breakdown.
When the team blocked caspase cleavage of nuclear lamin proteins, ROCK I activity altered nuclear morphology but wasn't sufficient to cause nuclear breakdown. Conversely, in cells lacking intact lamin proteins, ROCK I activation was enough to break apart the nucleus.
The team concludes that nuclear breakdown requires two cellular processes: contraction of the actin-myosin cytoskeleton, which results from ROCK I activation, and caspase cleavage of lamin proteins. What isn't yet clear is how the actin cytoskeleton links to the nuclear membrane. 
Rbiya S. Tuma
rabiya{at}nasw.org
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Actin-myosin–based contraction is responsible for apoptotic nuclear disintegration
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