Secreted phosphoprotein 1 binds integrins to initiate multiple cell signaling pathways, including FRAP1/mTOR, to support attachment and force-generated migration of trophectoderm cells.
Attachment and migration of trophectoderm (Tr) cells, hallmarks of blastocyst implantation in mammals, are unique uterine events. Secreted phosphoprotein 1 (SPP1) in the uterus binds integrins on conceptus Tr and uterine luminal epithelium (LE), affecting cell-cell and cell-matrix interactions. The signal transduction pathways activated by SPP1 and integrins in conceptuses have not been elucidated. Results of this study demonstrate that SPP1 binds alphavbeta3 and alpha5beta1 integrins to induce focal adhesion assembly, a prerequisite for adhesion and migration of Tr, through activation of: 1) P70S6K via crosstalk between FRAP1/mTOR and MAPK pathways; 2) mTOR, PI3K, MAPK3/MAPK1 (Erk1/2) and MAPK14 (p38) signaling to stimulate Tr cell migration; and 3) focal adhesion assembly and myosin II motor activity to induce migration of Tr cells. These cell signaling pathways, acting in concert, mediate adhesion, migration and cytoskeletal remodeling of Tr cells essential for expansion and elongation of conceptuses and attachment to uterine LE for implantation.
Kim
Jinyoung
J
Center for Animal Biotechnology and Genomics, Texas A&M University, College Station, TX 77843, USA.
Erikson
David W
DW
Burghardt
Robert C
RC
Spencer
Thomas E
TE
Wu
Guoyao
G
Bayless
Kayla J
KJ
Johnson
Greg A
GA
Bazer
Fuller W
FW
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002846:Chromatography, Affinity; D010064:Embryo Implantation / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D047468:Immunoprecipitation; D039081:Integrin alpha5beta1 / Q000502:physiology*; D039302:Integrin alphaVbeta3 / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D008856:Microscopy, Fluorescence; D053495:Osteopontin / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000502:physiology; D012756:Sheep; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D014599:Uterus / Q000201:enzymology / Q000502:physiology*
D004791:Enzyme Inhibitors; D007093:Imidazoles; D039081:Integrin alpha5beta1; D039302:Integrin alphaVbeta3; D047908:Intracellular Signaling Peptides and Proteins; D053495:Osteopontin; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011725:Pyridines; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C093642:SB 203580