Oocyte maturation is triggered by sperm-derived polypeptides known as major sperm proteins (MSPs), which activate the oocyte mitogen-activated protein kinase (MPK-1) ( Miller, 2001 Yang et al., 2010). The oocyte adjacent to the spermatheca undergoes oocyte maturation ~25 min before being ovulated into the spermatheca ( Greenstein, 2005). About 150 sperm are stored in each spermatheca, whereas the oocytes form in the oviduct in each gonad arm. elegans hermaphrodites produce sperm during the L4 larval stage and then shift to produce oocytes during the adult stage. elegans reproductive system consists of two U-shaped gonad arms, each ending with a spermatheca and joined in the center by a shared uterus. elegans contains multiple tubular tissues, including the reproductive system, that experience mechanical stimulation ( Cram, 2014 Cram, 2015 Voglis and Tavernarakis, 2005). However, the cellular and molecular mechanisms of PIEZO dysfunction in these diseases are not well understood.Ĭaenorhabditis elegans is an attractive model system for the study of mechanotransduction in vivo. Loss-of-function mutations in the PIEZO1 gene cause autosomal recessive congenital lymphatic dysplasia, whereas gain-of-function mutations lead to autosomal dominant stomatocytosis ( Alper, 2017). Mutations in both human PIEZO1 and human PIEZO2 have been identified among patients suffering from channelopathy diseases, such as dehydrated hereditary stomatocytosis (DHSt), generalized lymphatic dysplasia (GLD), and distal arthrogryposis type 5 (DA5), in which osmoregulation is disturbed ( Albuisson et al., 2013 Andolfo et al., 2013 Bae et al., 2013 Coste et al., 2013 Li et al., 2018 Lukacs et al., 2015 McMillin et al., 2014 Zarychanski et al., 2012). PIEZO2 primarily functions as a key mechanotransducer for light touch, proprioception and breathing ( Nonomura et al., 2017 Woo et al., 2015 Woo et al., 2014). Stem cells also use PIEZO1 to sense mechanical signals and to initiate Ca 2+ signaling to promote proliferation and differentiation ( Del Mármol et al., 2018 He et al., 2018). PIEZO1 also regulates vascular branching and endothelial cell alignment upon sensing frictional force (shear stress) ( Li et al., 2015 Nonomura et al., 2018). Recent studies have shown that the human and mouse PIEZO1 channels respond to different mechanical stimuli, including static pressure, shear stress and membrane stretch ( Coste et al., 2010 Poole et al., 2014 Ranade et al., 2014).
PIEZO1 is a non-selective ion channel that forms homotrimeric complexes at the plasma membrane however, PIEZO1 exhibits a preference for Ca 2+ in response to mechanical stimuli ( Coste et al., 2010 Gnanasambandam et al., 2015 Syeda et al., 2015). PIEZO1 and PIEZO2 are newly identified excitatory mechanosensitive proteinsthat play important roles in a wide range of developmental and physiological processes in mammals ( Alper, 2017 Coste et al., 2010 Coste et al., 2012 Murthy et al., 2017 Wu et al., 2017). Mechanotransduction - the sensation and conversion of mechanical stimuli into biological signals - is essential for development. These findings suggest that PEZO-1 acts in different reproductive tissues to promote proper ovulation and fertilization in C.
Loss of PEZO-1 also led to an inability of self-sperm to navigate back to the spermatheca properly after being pushed out of the spermatheca during ovulation. However, the calcium signaling was not dramatically changed in the pezo-1 mutants during ovulation. Post-ovulation oocytes were frequently damaged during spermathecal contraction. In vivo observations showed that oocytes undergo a variety of transit defects as they enter and exit the spermatheca during ovulation. A number of deletion alleles, as well as a putative gain-of-function mutant, of PEZO-1 caused a severe reduction in brood size. In this study, we discovered the vital roles of pezo-1, the sole PIEZO ortholog in Caenorhabditiselegans, in regulating reproduction. PIEZO1 and PIEZO2 are newly identified mechanosensitive ion channels that exhibit a preference for calcium in response to mechanical stimuli.
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