The C-terminal tail region of nonmuscle myosin II directs isoform-specific distribution in migrating cells.
Nonmuscle myosin II isoforms A and B (hereafter, IIA and IIB) perform unique roles in cell migration, even though both isoforms share the same basic molecular functions. That IIA and IIB assume distinct subcellular distribution in migrating cells suggests that discrete spatiotemporal regulation of each isoform's activity may provide a basis for its unique migratory functions. Here, we make the surprising finding that swapping a small C-terminal portion of the tail between IIA and IIB inverts the distinct distribution of these isoforms in migrating cells. Moreover, swapping this region between isoforms also inverts their specific turnover properties, as assessed by fluorescence recovery after photobleaching and Triton solubility. These data, acquired through the use of chimeras of IIA and IIB, suggest that the C-terminal region of the myosin heavy chain supersedes the distinct motor properties of the two isoforms as the predominant factor directing isoform-specific distribution. Furthermore, our results reveal a correlation between isoform solubility and distribution, leading to the proposal that the C-terminal region regulates isoform distribution by tightly controlling the amount of each isoform that is soluble and therefore available for redistribution into new protrusions.
Department of Pharmacology and Cancer Biology, Duke University Medical Center; Durham, NC 27710, USA.
Joshua C
JC
Sandquist
Anthony R
AR
Means
D000577:Amides; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D036681:Fluorescence Recovery After Photobleaching; D006576:Heterocyclic Compounds, 4 or More Rings / Q000378:metabolism; D006801:Humans; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D024507:Nonmuscle Myosin Type IIA / Q000235:genetics / Q000378:metabolism*; D024501:Nonmuscle Myosin Type IIB / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D011725:Pyridines; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D000577:Amides; D004791:Enzyme Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; D020033:Protein Isoforms; D011725:Pyridines; D011993:Recombinant Fusion Proteins; C108830:Y 27632; C472645:blebbistatin; D024507:Nonmuscle Myosin Type IIA; D024501:Nonmuscle Myosin Type IIB; D018995:Myosin Heavy Chains