Rapid de-localization of actin leading edge components with BDM treatment.
BACKGROUND
2,3-butanedione monoxime (BDM) has been widely used as a non-muscle myosin inhibitor to investigate the role of non-muscle myosinII in the process of actin retrograde flow and other actin cytoskeletal processes. Recent reports show that BDM does not inhibit any non-muscle myosins so far tested, including nm-myosinII, prompting the question, how were these process affected in BDM studies?


RESULTS
We have found that treatment of mammalian cells with BDM for only 1 min blocks actin incorporation at the leading edge in a permeabilized cell system. We show that inhibition of actin incorporation occurs through de-localization of leading edge proteins involved in actin polymerization--the Arp2/3 complex, WAVE, and VASP--that de-localize concomitantly with the leading edge actin network.


CONCLUSIONS
De-localization of actin leading edge components by BDM treatment is a newly described effect of this compound. It may explain many of the results previously ascribed to inhibition of non-muscle myosinII by BDM, particularly in studies of leading edge dynamics. Though this effect of BDM is intriguing, future studies probing actin dynamics at the leading edge should use more potent and specific inhibitors.
Yarrow
Justin C
JC
Dept of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA. jyarrow@hms.harvard.edu
Lechler
Terry
T
Li
Rong
R
Mitchison
Timothy J
TJ
D051378:Actin-Related Protein 3; D000199:Actins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007668:Kidney / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D024462:Myosin Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D041701:Swiss 3T3 Cells / Q000737:chemistry / Q000187:drug effects; D051300:Wiskott-Aldrich Syndrome Protein Family; D000098662:Vasodilator-Stimulated Phosphoprotein
D051378:Actin-Related Protein 3; D000199:Actins; C495929:Actr3 protein, mouse; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; C495774:Wasf1 protein, mouse; D051300:Wiskott-Aldrich Syndrome Protein Family; D000098662:Vasodilator-Stimulated Phosphoprotein; C004717:diacetylmonoxime; D024462:Myosin Type II; D003931:Diacetyl