Low density lipoprotein receptor-related protein 1 couples β1 integrin activation to degradation.

Low density lipoprotein receptor-related protein 1 couples β1 integrin activation to degradation.
Cell Mol Life Sci. 2017 Nov 07;:
Authors: Wujak L, Böttcher RT, Pak O, Frey H, El Agha E, Chen Y, Schmitt S, Bellusci S, Schaefer L, Weissmann N, Fässler R, Wygrecka M
Abstract
Low density lipoprotein receptor-related protein (LRP) 1 modulates cell adhesion and motility under normal and pathological conditions. Previous studies documented that LRP1 binds several integrin receptors and mediates their trafficking to the cell surface and endocytosis. However, the mechanism by which LRP1 may regulate integrin activation remains unknown. Here we report that LRP1 promotes the activation and subsequent degradation of β1 integrin and thus supports cell adhesion, spreading, migration and integrin signaling on fibronectin. LRP1 interacts with surface β1 integrin, binds the integrin activator kindlin2 and stimulates β1 integrin-kindlin2 complex formation. Specifically, serine 76 in the LRP1 cytoplasmic tail is crucial for the interaction with kindlin2, β1 integrin activation and cell adhesion. Interestingly, a loss of LRP1 induces the accumulation of several integrin receptors on the cell surface. Following internalization, intracellular trafficking of integrins is driven by LRP1 in a protein kinase C- and class II myosin-dependent manner. Ultimately, LRP1 dictates the fate of endocytosed β1 integrin by directing it down the pathway of lyso...

Source: Cellular and Molecular Life Sciences : CMLS - November 7, 2017 Category: Cytology Authors: Wujak L, Böttcher RT, Pak O, Frey H, El Agha E, Chen Y, Schmitt S, Bellusci S, Schaefer L, Weissmann N, Fässler R, Wygrecka M Tags: Cell Mol Life Sci Source Type: research