SKAP2 regulates Arp2/3 complex for actin-mediated asymmetric cytokinesis by interacting with WAVE2 in mouse oocytes

Abstract

SKAP2 (Src kinase-associated phosphoprotein 2), a substrate of Src family kinases, has been suggested to be involved in actin-mediated cellular processes. However, little is known about its role in mouse oocyte maturation. In this study, we thus investigated the expression, localization, and functions of SKAP2 during mouse oocyte asymmetric division. SKAP2 protein expression was detected at all developmental stages in mouse oocytes. Immunofluorescent staining showed that SKAP2 was mainly distributed at the cortex of the oocytes during maturation. Treatment with cytochalasin B in oocytes confirmed that SKAP2 was co-localized with actin. Depletion of SKAP2 by injection with specific short interfering RNA caused failure of spindle migration, polar body extrusion, and cytokinesis defects. Meanwhile, the staining of actin filaments at the oocyte membrane and in the cytoplasm was significantly reduced after these treatments. SKAP2 depletion also disrupted actin cap and cortical granule-free domain formation, and arrested a large proportion of oocytes at the telophase stage. Moreover, Arp2/3 complex and WAVE2 expression was decreased after the depletion of SKAP2 activity. Our results indicate that SKAP2 regulates the Arp2/3 complex and is essential for actin-mediated asymmetric cytokinesis by interacting with WAVE2 in mouse oocytes.

SKAP2 acts downstream of CD11b/CD18 and regulates neutrophil effector function

“…A previous study in mice suggests that phosphorylation of SKAP2 releases its binding to Wave2 and Cortactin, allowing for actin polymerization to proceed ( 38 , 76 ). Supporting findings demonstrated that Skap2 negatively regulates the integrin conformational change in murine neutrophils ( 57 ) and associates with actin rearrangement in endothelial cells ( 77 ), a step required for adhesion and extravasation after TNF-mediated recruitment.…”

Polo-like kinase 1 promotes Cdc42-induced actin polymerization for asymmetric division in oocytes

“…The fact that Plk1 inhibitors prevented N-Wasp recovery to a greater extent than actin suggests that additional actin polymerization pathways may be present that can act redundantly with N-Wasp. In this context deletion of N-Wasp from oocytes does not abolish actin polymerization [46] and downregulation of other family members, WAVE and WASH, have been shown to suppress polar body formation [24,47,48]. More work is needed to know if the WAVE/WASH knock-down phenotype is caused by severe effects on spindle organization or via a direct effect on actin polymerization.…”

miRNA expression profiles of peripheral white blood cells from beef heifers with varying reproductive potential

“…SKAP2 and CLEC4D were associated with regulating the immune response pathway in the FH group. SKAP2 is a substrate of Src family kinase and regulates cellular processes, including proliferation, adhesion, migration and stress response ( He et al, 2017 ). In a previous study, SKAP2 was detected in all developmental stages of mouse oocytes and depletion of SKAP2 caused the failure of spindle migration, polar body extrusion and cytokinesis defects ( He et al, 2017 ).…”

“…SKAP2 is a substrate of Src family kinase and regulates cellular processes, including proliferation, adhesion, migration and stress response ( He et al, 2017 ). In a previous study, SKAP2 was detected in all developmental stages of mouse oocytes and depletion of SKAP2 caused the failure of spindle migration, polar body extrusion and cytokinesis defects ( He et al, 2017 ). In a separate study in sheep, SKAP2 was differentially expressed in the granulosa cells from superstimulated lamb and ewe follicles and was associated with cellular growth, proliferation, and migration ( Wu et al, 2016 ).…”