NCBI Summary:
This gene encodes a cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Alternatively spliced transcript variants encoding different isoforms have been described for this gene. These isoforms exhibit different expression pattern, and have different biochemical, as well as physiological properties (PMID:9054445). [provided by RefSeq, Aug 2011]
General function
Cytoskeleton organization
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Cellular localization
Cytoskeleton
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Ovarian function
Follicle atresia
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Androgens regulate ovarian follicular development by increasing follicle stimulating hormone receptor and microRNA-125b expression. Sen A 2014 et al.
Although androgen excess is considered detrimental to women's health and fertility, global and ovarian granulosa cell-specific androgen-receptor (AR) knockout mouse models have been used to show that androgen actions through ARs are actually necessary for normal ovarian function and female fertility. Here we describe two AR-mediated pathways in granulosa cells that regulate ovarian follicular development and therefore female fertility. First, we show that androgens attenuate follicular atresia through nuclear and extranuclear signaling pathways by enhancing expression of the microRNA (miR) miR-125b, which in turn suppresses proapoptotic protein expression. Second, we demonstrate that, independent of transcription, androgens enhance follicle-stimulating hormone (FSH) receptor expression, which then augments FSH-mediated follicle growth and development. Interestingly, we find that the scaffold molecule paxillin regulates both processes, making it a critical regulator of AR actions in the ovary. Finally, we report that low doses of exogenous androgens enhance gonadotropin-induced ovulation in mice, further demonstrating the critical role that androgens play in follicular development and fertility. These data may explain reported positive effects of androgens on ovulation rates in women with diminished ovarian reserve. Furthermore, this study demonstrates mechanisms that might contribute to the unregulated follicle growth seen in diseases of excess androgens such as polycystic ovary syndrome.
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Expression regulated by
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Ovarian localization
Oocyte, Granulosa
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Paxillin and steroid signaling: from frog to human. Hammes SR 2014 et al.
Paxillin is a well-characterized cytoplasmic adaptor protein that is known to play important roles in cytoskeletal rearrangement, cell adhesion, and cell motility. In addition to its structural functions, paxillin has more recently been shown to function as a regulator of cell division-mediating steroid-triggered meiosis in oocytes as well as steroid- and growth factor-induced proliferation in prostate and breast cancer. Paxillin mediates these processes through a conserved pathway that involves both extranuclear (nongenomic) and nuclear (genomic) steroid signaling, as well as both cytoplasmic and nuclear kinase signaling. In fact, paxillin appears to serve as a critical liaison between extranuclear and nuclear signaling in response to multiple stimuli, making it a fascinating molecule to study when trying to determine how growth signals from the membrane lead to important proliferative changes in the nucleus. This chapter outlines recent advances in understanding how paxillin regulates both steroid and growth factor signaling, focusing on the conserved nature of its actions from a frog germ cell to a human cancer cell.
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