Role of SVIL phosphorylation by PLK1 in myosin II activation and cytokinetic furrowing

Abstract

SummaryPolo-like kinase 1 (PLK1) is a widely conserved serine/threonine kinase that regulates progression of multiple stages of mitosis. Although extensive studies about PLK1 functions during cell division have been performed, it is still not known how PLK1 regulates myosin II activation at the equatorial cortex and ingression of the cleavage furrow. In this report, we show that an actin/myosin-IIbinding protein, supervillin (SVIL), is a substrate of PLK1. PLK1 phosphorylates Ser238 of SVIL, which can promote the localization of SVIL to the central spindle and association with PRC1. Expression of a PLK1 phosphorylation site mutant, S238A-SVIL, inhibited myosin II activation at the equatorial cortex and induced aberrant furrowing. SVIL has both actin-and myosin-II-binding regions in the N-terminus. Expression of DMyo-SVIL (deleted of the myosin-II-binding region), but not of DAct-SVIL (deleted of actin-binding region), reduced myosin II activation and caused defects in furrowing. Our study indicates a possible role of phosphorylated SVIL as a molecular link between the central spindle and the contractile ring to coordinate the activation of myosin II for the ingression of the cleavage furrow.

Supervillin binding to myosin II and synergism with anillin are required for cytokinesis

“…Furthermore, the second region of supervillin important for normal cell division (SV-831–1281) contains the KIF14-interaction site (Smith et al. , 2010) and potentially a binding site for PRC1 (Hasegawa et al. , 2013), both of which are required for central spindle assembly (Carleton et al.…”

Hyaluronan and RHAMM in Wound Repair and the “Cancerization” of Stromal Tissues

“…Supervillin, a membrane bound actin binding protein that participates in myosin II mediated contractility, interacts with calponin and regulates the activity of another RHAMM binding partner, ERK1,2 [194]. Supervillin coordinates processes that require dynamic cytoskeleton and membrane turnover including cell migration and cytokinesis [193, 195]. Indeed, RHAMM−/− cells often undergo aberrant cytokinesis causing the formation of multinucleated cells [165].…”

Plk1 inhibition leads to a failure of mitotic division during the first mitotic division in pig embryos

“…The multifunctionality of Plk1 is coupled with its dynamic subcellular localization during mitotic division [3,4]. Plk1, primarily located in the centrosome and kinetochore during prophase, shifts to the spindle intermediate region in meta-anaphase and then concentrates at the equatorial plate during cytokinesis [5,6]. Plk1 consists of an N-terminal kinase domain and a phosphorylation sequence of the C-terminal Polo box domain (PBD) [7,8].…”

“…Plk1 consists of an N-terminal kinase domain and a phosphorylation sequence of the C-terminal Polo box domain (PBD) [7,8]. It is mainly located in different subcellular structures based on the PBD and phosphorylation of Thr 210 [1,5]. It is involved in the regulation of Mps1, Bub3, Mad1, and other proteins [9].…”