A Naturally Occurring Lgr4 Splice Variant Encodes a Soluble Antagonist Useful for Demonstrating the Gonadal Roles of Lgr4 in Mammals

Autor: Masataka Kudo, Aaron J. W. Hsueh, Pei Jen Hsu, Ching Wei Luo, Fang Ju Wu, Chih Lun Hsiao
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Sexual Reproduction
Male
Physiology
Organogenesis
lcsh:Medicine
Gene Expression
Biochemistry
Receptors
G-Protein-Coupled
Mice
Cell Signaling
Testis
Medicine and Health Sciences
Lipid Hormones
Receptor
lcsh:Science
Progesterone
Multidisciplinary
Pharmaceutics
luteinizing hormone/choriogonadotropin receptor
Wnt signaling pathway
Gene Expression Regulation
Developmental
Beta-Catenin Signaling
Receptors
LH
Cell biology
WNT Coreceptors
Ectodomain
Aquaporin 1
Female
Signal transduction
Coreceptors
Research Article
Signal Transduction
Testes Development
Ovulation
medicine.medical_specialty
Molecular Sequence Data
Nerve Tissue Proteins
Biology
Drug Therapy
Internal medicine
medicine
Genetics
Reproductive Endocrinology
Animals
Humans
Amino Acid Sequence
Eye Proteins
RSPO2
Biology and life sciences
Endocrine Physiology
lcsh:R
Ovary
Estrogen Receptor alpha
Cell Biology
Hormones
Rats
Alternative Splicing
Endocrinology
HEK293 Cells
RNA processing
Animals
Newborn
Ovary Development
RNA
lcsh:Q
Cattle
Physiological Processes
Thrombospondins
Estrogen receptor alpha
Organism Development
Sequence Alignment
Receptor Antagonist Therapy
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 9, Iss 9, p e106804 (2014)
ISSN: 1932-6203
Popis: Leucine-rich repeat containing G protein-coupled receptor 4 (LGR4) promotes the Wnt signaling through interaction with R-spondins or norrin. Using PCR amplification from rat ovarian cDNAs, we identified a naturally occurring Lgr4 splice variant encoding only the ectodomain of Lgr4, which was named Lgr4-ED. Lgr4-ED can be detected as a secreted protein in the extracts from rodent and bovine postnatal gonads, suggesting conservation of Lgr4-ED in mammals. Recombinant Lgr4-ED purified from the conditioned media of transfected 293T cells was found to dose-dependently inhibit the LGR4-mediated Wnt signaling induced by RSPO2 or norrin, suggesting that it is capable of ligand absorption and could have a potential role as an antagonist. Intraperitoneal injection of purified recombinant Lgr4-ED into newborn mice was found to significantly decrease the testicular expression of estrogen receptor alpha and aquaporin 1, which is similar to the phenotype found in Lgr4-null mice. Administration of recombinant Lgr4-ED to superovulated female rats can also decrease the expression of estrogen receptor alpha, aquaporin 1, LH receptor and other key steroidogenic genes as well as bring about the suppression of progesterone production. Thus, these findings suggest that endogenously expressed Lgr4-ED may act as an antagonist molecule and help to fine-tune the R-spondin/norrin-mediated Lgr4-Wnt signaling during gonadal development.
Databáze: OpenAIRE
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