The role of LRP1 in beta-1-integrin endocytosis
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Abstract
The LRP1 is a major cell surface endocytic receptor and can bind to more than 40 different intracellular and extracellular ligands. LRP1 previously has been shown to interact with the extracellular matrix (ECM)-binding protein β1-integrin and to influence its maturation. β1-integrin as a heterodimeric receptor connects the actin cytoskeleton with the exterior ECM.
In order to unravel the potential interplay between LRP1 and β1-integrin a model system with a substitution of the LRP1 NPxY2 motif by a multiple alanine cassette was mainly used in this study. Co-immunoprecipitation experiments validated a potential interaction of LRP1 and β1-integrin dependent on a functional NPxY2 motif of LRP1. Coupled endocytosis of LRP1 and β1-integrin was observed, which influenced cellular processes such as adhesion and spreading. The lack of joined LRP1 and β1-integrin internalization altered the dynamics of focal adhesion (FA) assembly and disassembly, resulting in reduced cell migration of MEF LRP1 NPxY2 ki cells. Similar results concerning cell migration and the actin cytoskeleton organization could be observed in the corresponding C57Bl6 LRP1 NPxY2 ki mouse model.
The results point to a functional interaction of LRP1 with β1-integrin in terms of coupled endocytosis, which affects actin cytoskeleton dependent cellular processes in vivo and in vitro.