In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2019-09-13)
Abstract:
Activated α 2 -macroglobulin (α 2 M*) and its receptor, low-density lipoprotein receptor-related protein 1 (LRP1), have been linked to proliferative retinal diseases. In Müller glial cells (MGCs), the α 2 M*/LRP1 interaction induces cell signaling, cell migration, and extracellular matrix remodeling, processes closely associated with proliferative disorders. However, the mechanism whereby α 2 M* and LRP1 participate in the aforementioned pathologies remains incompletely elucidated. Here, we investigate whether α 2 M* regulates both the intracellular distribution and sorting of LRP1 to the plasma membrane (PM) and how this regulation is involved in the cell migration of MGCs. Using a human Müller glial-derived cell line, MIO-M1, we demonstrate that the α 2 M*/LRP1 complex is internalized and rapidly reaches early endosomes. Afterward, α 2 M* is routed to degradative compartments, while LRP1 is accumulated at the PM through a Rab10-dependent exocytic pathway regulated by PI3K/Akt. Interestingly, Rab10 knockdown reduces both LRP1 accumulation at the PM and cell migration of MIO-M1 cells induced by α 2 M*. Given the importance of MGCs in the maintenance of retinal homeostasis, unravelling this molecular mechanism can potentially provide new therapeutic targets for the treatment of proliferative retinopathies.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-019-49072-6
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2019
detail.hit.zdb_id:
2615211-3
Permalink
