| First Author | Rabiej VK | Year | 2016 |
| Journal | Exp Cell Res | Volume | 340 |
| Issue | 1 | Pages | 102-15 |
| PubMed ID | 26610862 | Mgi Jnum | J:229550 |
| Mgi Id | MGI:5752431 | Doi | 10.1016/j.yexcr.2015.11.020 |
| Citation | Rabiej VK, et al. (2016) Low density lipoprotein receptor-related protein 1 mediated endocytosis of beta1-integrin influences cell adhesion and cell migration. Exp Cell Res 340(1):102-15 |
| abstractText | The low density lipoprotein receptor-related protein 1 (LRP1) has been shown to interact with beta1-integrin and regulate its surface expression. LRP1 knock-out cells exhibit altered cytoskeleton organization and decreased cell migration. Here we demonstrate coupled endocytosis of LRP1 and beta1-integrin and the involvement of the intracellular NPxY2 motif of LRP1 in this process. Mouse embryonic fibroblasts harboring a knock in replacement of the NPxY2 motif of LRP1 by a multiple alanine cassette (AAxA) showed elevated surface expression of beta1-integrin and decreased beta1-integrin internalization rates. As a consequence, cell spreading was altered and adhesion rates were increased in our cell model. Cells formed more focal adhesion complexes, whereby in vitro cell migration rates were decreased. Similar results could be observed in a corresponding mouse model, the C57Bl6 LRP1 NPxYxxL knock in mice, therefore, the biochemistry of cellular adhesion was altered in primary cortical neurons. In vivo cell migration experiments demonstrated a disturbance of neuroblast cell migration along the rostral migratory stream. In summary, our results indicate that LRP1 interacts with beta1-integrin mediating integrin internalization and thus correlates with downstream signaling of beta1-integrin such as focal adhesion dynamics. Consequently, the disturbance of this interaction resulted in a dysfunction in in vivo and in vitro cell adhesion and cell migration. |
