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Dynamics of Actin‐based Structures in Migrating Artery Myocytes are Regulated by Phosphodiesterases
Author(s) -
Brzezinska Paulina,
McBride Ainslie,
Mackeil Jodi,
Maurice Donald
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.783.3
Subject(s) - forskolin , phosphodiesterase 3 , adenylyl cyclase , microbiology and biotechnology , phosphodiesterase , myocyte , actin , cell migration , chemistry , biology , biochemistry , signal transduction , cell , in vitro , enzyme
The second messenger, cAMP, regulates vascular myocyte migration dichotomously. Indeed, while cAMP inhibits vascular myocyte migration in vitro and reduces intimal hyperplasia in vivo , it also promotes formation of integrin‐based, actin‐rich, leading edge projections in these cells; structures which are essential for migration. Our study was undertaken to examine if distinct cyclic nucleotide phosphodiesterases (PDEs) could modulate formation of such actin‐rich projections in migrating mammary artery myocytes (MAM). Thus, we quantified formation of leading edge, actin‐rich, structures in these cells and assessed how inhibiting or knocking down selected MAM PDEs (PDE1, PDE3 or PDE4) impacted their formation. In the absence of adenylyl cyclase activation, formation of these structures was promoted when either PDE1, or PDE4, were selectively inhibited using C‐33 or Ro, 20‐1724, respectively. PDE3 selective inhibition with cilostamide was without effect. In marked contrast, when added with forskolin, an adenylyl cyclase activator, PDE1, PDE3 or PDE4 inhibitors each potentiated the ability of forskolin to reduce formation of the actin‐based structures. Knockdown of PDE1C or PDE4D, recapitulated effects observed with the enzyme inhibitors both in the absence and presence of forskolin. These data are consistent with the notion that localized cAMP “pools” regulated by PDE1 and/or PDE4 enzymes at the leading edges of migrating cells can promote formation of actin‐based adhesive structures, but that these events are poorly supported in cells in which cAMP is globally increased.