Focal adhesion kinase localizes to sites of cell‐to‐cell contact in vivo and increases apically in rat uterine luminal epithelium and the blastocyst at the time of implantation

Abstract

Focal adhesions play an important role in promoting embryo invasion; in particular, focal adhesions disassemble at the time of implantation in the rat, facilitating the detachment of the uterine luminal epithelium to allow the embryo to invade the endometrium. This study investigated focal adhesion protein, focal adhesion kinase (FAK) in the rat uterine luminal, and glandular epithelial cells to understand the dynamics of focal adhesions during early pregnancy. FAK undergoes extensive distributional change during early pregnancy, and surprisingly, FAK was not localized at the site of focal adhesions, instead being localized to the site of cell-to-cell contact and colocalizing with ZO-1 on day 1 of pregnancy. At the time of implantation, FAK increases in the apical region of the uterine luminal epithelial cells which was regulated by progesterone. Using an in vitro co-culture model of rat blastocysts attached to Ishikawa cells, FAK was present apically both in the rat blastocyst and the Ishikawa cells, suggesting a role in attachment andin mediating signal transduction between these two genetically different cell types.

Integrin beta8 (ITGB8) activates VAV-RAC1 signaling via FAK in the acquisition of endometrial epithelial cell receptivity for blastocyst implantation

“…Surprisingly, the isolated and cultured endometrial epithelial cells mirrored the effect as seen under the in vivo conditions, suggesting the acquisition of FAK activity in the development of receptivity of the endometrium. The cellular distribution pattern of FAK was mostly in the apical region during the pre-receptive stage and during the advance stage, the localization of FAK became prominent in the basal region of endometrial epithelial cells, which very well correlated with the earlier observations 32 . Interestingly, FAK inhibition in the uterus during receptivity phase can render the poor implantation of the blastocyst (sites).…”

“…FAK is one of the important players during embryo invasion and expressed in the uterine luminal, glandular epithelial cells 32 . Focal adhesion kinase (FAK) is a central protein tyrosine kinase (PTK) involved in integrin signaling 33 and during its activation, FAK gets phosphorylated at Y397 residue.…”

mTOR signalling, embryogenesis and the control of lung development

“…SPP1 interaction with the trophoblast integrin heterodimer aVb6 and uterine epithelial integrin aVb3 induces focal adhesion molecule assembly that may be particularly essential for stabilising embryo implantation and trophoblast invasion of the uterine stroma [46]. From here, focal adhesion kinase (FAK) orchestrates PI3K, Akt, mTOR, ERK1/2 and p38 MAPK signalling to regulate temporal cell adhesion and cytoskeletal remodelling during cytokinesis and trophoblast expansion [47,48]. mTOR is implicated during this time as a link between paracrine and nutrient cues that influence trophoblast cell growth.…”

Uterine molecular changes for non‐invasive embryonic attachment in the marsupials Macropus eugenii (Macropodidae) and Trichosurus vulpecula (Phalangeridae)

“…Marsupial species likely achieve non‐invasive embryonic attachment by utilizing a variety of uterine strategies to exclude the embryo. Additional strategies may involve redistribution of other focal adhesion molecules, including integrins and focal adhesion kinases, which play important structural and signalling roles in rodents, humans, and pigs (Burkin et al, ; Garlow et al, ; Kaneko, Lecce, Day, & Murphy, ). Alterations to lateral adhesion between adjacent epithelial cells may also be involved.…”