Identification of LRP-1 as an endocytosis and recycling receptor for β1-integrin in thyroid cancer cells

authors

  • Theret Louis
  • Jeanne Albin
  • Langlois Benoit
  • Hachet Cathy
  • David Marion
  • Khrestchatisky Michel
  • Devy Jérôme
  • Hervé Emonard
  • Almagro Sébastien
  • Dedieu Stéphane

keywords

  • Cancer
  • Endocytosis
  • LRP-1
  • Recycling
  • Β1-integrin

abstract

LRP-1 is a large endocytic receptor mediating the clearance of various molecules from the extracellular matrix. LRP-1 was reported to control focal adhesion turnover to optimize the adhesion-deadhesion balance to support invasion. To better understand how LRP-1 coordinates cell-extracellular matrix interface, we explored its ability to regulate cell surface integrins in thyroid carcinomas. Using an antibody approach, we demonstrated that β1-integrin levels were increased at the plasma membrane underLRP1silencing or upon RAP treatment, used as LRP-1 antagonist. Our data revealed that LRP-1 binds with both inactive and active β1-integrin conformations and identified the extracellular ligand-binding domains II or IV of LRP-1 as sufficient to bind β1-integrin. Using a recombinant β1-integrin, we demonstrated that LRP-1 acts as a regulator of β1-integrin intracellular traffic. Moreover, RAP or LRP-1 blocking antibodies decreased up to 36% the number of β1-integrin-containing endosomes. LRP-1 blockade did not significantly affect the levels of β1-integrin-containing lysosomes while decreasing localization of β1-integrin within Rab-11 positive vesicles. Overall, we identified an original molecular process in which LRP-1 acts as a main regulator of β1-integrin internalization and recycling in thyroid cancer cells.

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