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Wnt signaling in spermatogenesis and male infertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Vertika Singh, Meghali Joshi, Kiran Singh, Rajender Singh
Frizzled receptors like GPCRs are seven-transmembrane proteins acting as the primary receptors for Wnt signaling. The Fz receptor consists of an extracellular cysteine-rich domain (CRD), which is the site of interaction with Wnt proteins (22). There are 10 FZD genes present in humans, numbered from FZD1 to FZD10. FZD proteins are divided into five subgroups: FZD1/2/7, FZD3/6, FZD5/8, FZD9/10 and FZD4 (23). Another family of receptors is called low-density lipoprotein-related receptors (LRPs), which are single-pass transmembrane proteins and are over 1,600 amino acids in size (24,25). LRP5 and LRP6 are the homologs of Drosophila Arrow protein (26). They are also important for signal transduction along with FZD receptors. This raised the possibility that FZD and LRP function as coreceptors for Wnt proteins. An interaction between Wnt and LRP has been seen, and a ternary complex is formed between Wnt and extracellular domains of FZD and LRP in mouse (25). It has been reported that the overexpression of the intracellular domain of LRP6 can activate the Wnt signaling constitutively, suggesting that the extracellular domain plays a regulatory role in controlling signal transduction. There are multiple phosphorylation sites present on the intracellular domain of LRP5/6. The phosphorylation of these sites is important for the initiation of the signal transduction through Wnt/β-catenin signaling. LRP6 is phosphorylated by many kinases either in a Wnt-dependent (G protein receptor kinase 5/6) or Wnt-independent (protein kinase A, PFTAIRE protein kinase 1) manner (27).
Human ESC-sEVs alleviate age-related bone loss by rejuvenating senescent bone marrow-derived mesenchymal stem cells
Published in Journal of Extracellular Vesicles, 2020
Liangzhi Gong, Bi Chen, Juntao Zhang, Yongjin Sun, Ji Yuan, Xin Niu, Guowen Hu, Yu Chen, Zongping Xie, Zhifeng Deng, Qing Li, Yang Wang
RNA-seq and bioinformatics analyses of sequencing data after hESC-sEVs treatment identified upregulated genes involved in bone cell proliferation and differentiation. This finding is consistent with the therapeutic effect of hESC-sEVs in promoting the proliferation and osteogenic differentiation of BM-MSCs. Importantly, GSEA analysis showed that hESC-sEVs treatment significantly activated the expression of genes involved in antiaging, stem cell proliferation and osteogenic differentiation. Among these genes, Sox9, Wnt4, Wnt10b, Wnt2b, Wnt6, and Fzd9 are associated with the Wnt signalling pathway and have been reported to enhance self-renewal and differentiation of MSCs as well as prevent skeletal ageing [37–39,49,50]. Pfkfb3, Nos and Cpt1b are Sirtuin signalling-related genes that have been demonstrated to promote cell cycle progression, suppress apoptosis, inhibit cellular ageing and stimulate bone regeneration [51–53]. Hmga2, Fgf21, Met and Tbx2 have been shown to protect against cellular senescence and promote stem cell proliferation [54–56]. In addition, Pdgfra and Fgfr2 are known to be essential for the osteogenic differentiation of BM-MSCs and bone formation [57,58]. Taken together, this evidence suggests that the therapeutic effect of hESC-sEVs in attenuating BM-MSC senescence is attributed to the activation of these antiaging and osteogenesis associated genes.
Molecular mechanisms that change synapse number
Published in Journal of Neurogenetics, 2018
Alicia Mansilla, Sheila Jordán-Álvarez, Elena Santana, Patricia Jarabo, Sergio Casas-Tintó, Alberto Ferrús
Receptors coupled to G proteins (GCPR) can modulate synapse activity. One of them is the metabotropic glutamate receptor (mGluR). The three component types of the G protein complex, α, β and γ, play a wide repertoire of regulatory activities. In cone photoreceptors of salamander retinas, activation of mGluR reduces Ca2+ influx and neurotransmission. However, both effects are mechanistically independent because the βγ dimer interacts with SNAP-25 to modulate synaptic vesicle fusion without altering significantly the Ca2+ influx (Van Hook et al., 2017). Other GPCRs, however, use the Gβγ dimer to elicit an increase of the Ca2+ influx and promote spinogenesis, as illustrated by Frizzled9 (FZD9) receptor upon binding to its ligand the growth factor Wnt-5a in hippocampal neurons (Ramirez, Ramos-Fernandez, Henriquez, Lorenzo, & Inestrosa, 2016). The mammalian Wnt is represented in Drosophila, where it was first identified, and named Wingless (wg). In both sets of species, this family of growth factors is involved in multiple functions including, segment polarity, cell differentiation, synapse maintenance and, when defective, may result in cancer or neurodegeneration (rev. Arnés & Casas-Tintó, 2017).
The Prenatal Diagnosis of Seven Fetuses with 7q11.23 Microdeletion or Microduplication
Published in Fetal and Pediatric Pathology, 2020
Yinghui Dang, Shanning Wan, Yunyun Zheng, Tingting Song, Chunyan Li, Yu Li, Jianfang Zhang
In cases 2, 3, 4, and 5 the karyotypes were normal. BoBs showed that all the 7q11.23 probes were shifted to the left, exceeding the system threshold, signifying 7q11.23 microdeletion syndrome (Fig. 1A). CMA indicated an approximately 1.5-Mb heterozygous microdeletion in 7q11.23 in four fetuses (Fig. 2A), suggesting that the results presented by CMA and BoBs were the same. The 7q11.23 region had an approximately 1.5-Mb microdeletion containing 23 OMIM genes, including NSUN5, FKBP6, FZD9, BAZ1B, BCL7B, MLXIPL, VPS37D, WBSCR22, STX1A, ABHD11, CLDN3, CLDN4, WBSCR27, WBSCR28, ELN, LIMK1, EIF4H, MIR590, LAT2, RFC2, CLIP2, GTF2IRD1, and GTF2I.