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Thrombospondin‐1 binds to ApoER2 and VLDL receptor and functions in postnatal neuronal migration
Author(s) -
Blake Sophia M,
Strasser Vera,
Andrade Nuno,
Duit Sarah,
Hofbauer Reinhold,
Schneider Wolfgang J,
Nimpf Johannes
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.223
Subject(s) - biology , receptor , thrombospondin , neuronal migration , microbiology and biotechnology , neuroscience , genetics , metalloproteinase , matrix metalloproteinase
Apolipoprotein E receptor 2 (ApoER2), very low‐density lipoprotein receptor (VLDLR), and Dab1 are the main components of the Reelin signalling cascade. Reelin is the sole ligand defined so far in signalling through this pathway. Postnatal migration of neuronal precursors from the subventricular zone (SVZ) to the olfactory bulb (OB), however, depends on ApoER2 and Dab1, but functions independently of Reelin. Here, we show that thrombospondin‐1 (THBS‐1) is a novel physiological ligand for ApoER2 and VLDLR. THBS‐1 is present in the SVZ and along the entire rostral migratory stream (RMS). It binds to ApoER2 and VLDLR and induces phosphorylation of Dab1. In contrast to Reelin, it does not induce Dab1 degradation or Akt phosphorylation, but stabilizes neuronal precursor chains derived from subventricular explants. Lack of THBS‐1 results in anatomical abnormalities of the RMS and leads to a reduction of postnatal neuronal precursors entering the OB.