G alpha-i2 in Ciliated Tissues: Physiological Role in Regulation of Ependymal Ciliary Function and Characteristics in Human Female Reproductive Tissues" (G alfa-i2-proteiini värekarvallisissa kudoksissa: Fysiologinen rooli ependyymisolujen värekarvojen toiminnan säätelyssä ja ominaispiirteet naisen lisääntymiskudoksissa)

Heterotrimeric G proteins are a family of guanine nucleotide-binding and catalysing proteins, which transduce extracellular signals from G protein-coupled receptors into the intracellular signalling pathways.Heterotrimeric G proteins consist of a, b and g subunits and take part in the regulation of various physiological processes such as cell growth, hormonal regulation, sensory perception and neuronal activity.Based on the structural and functional differences between the a subunits, G proteins are classified in different families, with the G i family being the most diverse.G i family subunit Ga i2 shows a ubiquitous distribution in rat and particular enrichment in ciliated cells in different tissues.The role of Ga i2 in peripheral tissues has been intensively studied, but the potential cilia-related role has remained unresolved.The aim of this study was t o c l a r i f y t h e p h y s i o l o g i c a l r o l e o f G a i2 i n r a t b r a i n e p e n d y m al c i l i a a n d to u n c o v e r t h e mechanisms controlling ependymal ciliary function.Furthermore, the study aimed to elucidate the characteristics of Ga i2 in ciliated reproductive tissues in human female.In order to clarify the role of Ga i2 in brain homeostasis, the function of the Ga i2 gene was silenced by using continuous in vivo antisense administration.The effect of Ga i2 knock-down and the effect of selected compounds on the ependymal ciliary function were studied using rat primary ependymal cell cultures.The presence of Ga i2 in human female reproductive tissues was studied using molecular biology tools and the localization of Ga i2 w a s v e r i f i e d b y immunohistochemistry.This study revealed a cilia-related physiological role for Ga i2 .The results showed that Ga i2 regulates CSF homeostasis in rat brain in vivo and ciliary beat frequency in rat brain ependymal cells in vitro.Further, this study revealed for the first time a receptor-mediated inhibition of ependymal ciliary function by PACAP27 and involvement of a cAMP-dependent pathway in the regulation of ciliary amplitude.Furthermore, this study unveiled the localization of Ga i2 in female reproductive tissues in human, including endometrium and Fallopian tube epithelium, with specific enrichment in the Fallopian tube cilia and endometrial glands.Ga i2 was shown to follow hormonal regulation during the menstrual cycle.Estradiol was shown to up-regulate Ga i2 gene expression in immortalised human oviductal epithelial cell line OE-E6/E7.In summ ary, Ga i2 has a cilia-relate d physiological role in rat brain and it is hormonally regulated in the human female reproductive tract.