Activated proline‐rich tyrosine kinase 2 regulates meiotic spindle assembly in the mouse oocyte

Abstract

Proline-rich tyrosine kinase 2 (PYK2), a member of the protein tyrosine kinase family, plays an important role in various cellular processes. PYK2 can be phosphorylated on tyrosine 402 by diverse stimuli at the cell surface, and recent studies have shown that this activated form of PYK2 is enriched in oocytes and required for fertilization. However, the subcellular localization and functions of activated PYK2 in oocytes remain elusive.In this study, we demonstrate that the localization of p-PYK2 undergoes dynamic changes during in vitro maturation of mouse oocytes. The signal of p-PYK2 is initially dispersed in the cytoplasm, but begins to decorate organized microtubules after the germinal vesicle breakdown and localizes to spindle poles at metaphase. Our data further show that p-PYK2 colocalizes with γ-tubulin from the germinal vesicle stage through the end of meiosis in mouse oocytes. Nocodazole treatment and washout experiments confirm that p-PYK2 associates with the oocyte spindle and spindle poles. Moreover, pharmacological inhibition of PYK2 activity dramatically alters the morphology of the bipolar spindle and prevents oocyte maturation. Together, these data suggest that activated PYK2 may function as a component of the microtubule organizing center to regulate spindle assembly during the meiotic process of mouse oocytes.

Ptk2b deletion improves mice folliculogenesis and fecundity via inhibiting follicle loss mediated by Erk pathway

“…However, for Ptk2b −/− mice, the number of matured oocytes was 191 oocytes from nine (over 21 oocytes per mice). After (Figure 3l-n), which was different with the previous in vitro results that the spindle assembly was disrupted when PTK2B was inhibited by its inhibitor (Meng et al, 2018).…”

“…Recently, it has been reported that PTK2B was localized to tubulin and its inhibition affects the spindle assembly and oocyte maturation in vitro (Meng et al, 2018). The expression pattern of Ptk2b during germ cell development also suggested that this gene might be crucial in mice fertility.…”

“…In males, Ptk2b has been reported to be expressed in mouse testis (Beverdam et al, 2010) or human sperm and involved in the signaling pathway downstream of protein kinase A during human sperm capacitation (Battistone et al, 2014; Brukman et al, 2019). In females, it has also been reported to be localized to microtubule organizing center or concentrated in cortical cytoskeleton of the oocytes, and played important roles in spindle assembly (Meng et al, 2018) or oocyte maturation (Meng et al, 2006). Moreover, some other studies also found that Ptk2b functioned during fertilization (McGinnis, Luo, & Kinsey, 2013; Meng et al, 2016) and the Ptk2b disruption prevented the incorporation of sperm to the ooplasm (Luo, McGinnis, Carlton, Beggs, & Kinsey, 2014; Wang, Luo, Carlton, McGinnis, & Kinsey, 2017).…”

“…In females, it has also been reported to be localized to microtubule organizing center or concentrated in cortical cytoskeleton of the Yanyan Cong and Haibo Wu contributed equally to this work. oocytes, and played important roles in spindle assembly (Meng et al, 2018) or oocyte maturation (Meng et al, 2006). Moreover, some other studies also found that Ptk2b functioned during fertilization (McGinnis, Luo, & Kinsey, 2013;Meng et al, 2016)…”

“Amyloid‐beta accumulation cycle” as a prevention and/or therapy target for Alzheimer's disease

“…May function as a component of the microtubule‐organizing center to regulate spindle assembly during the meiotic process of mouse oocytes (Meng et al, ),…”