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Tubby and tubby‐like protein 1 are new MerTK ligands for phagocytosis
Author(s) -
Caberoy Nora B,
Zhou Yixiong,
Li Wei
Publication year - 2010
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.2010.265
Subject(s) - biology , mertk , phagocytosis , genetics , microbiology and biotechnology , signal transduction , receptor tyrosine kinase
Tubby and tubby‐like protein 1 (Tulp1) are newly identified phagocytosis ligands to facilitate retinal pigment epithelium (RPE) and macrophage phagocytosis. Both proteins without classical signal peptide have been demonstrated with unconventional secretion. Here, we characterized them as novel MerTK ligands to facilitate phagocytosis. Tulp1 interacts with T yro3, A xl and M erTK of the TAM receptor tyrosine kinase subfamily, whereas tubby binds only to MerTK. Excessive soluble MerTK extracellular domain blocked tubby‐ or Tulp1‐mediated phagocytosis. Both ligands induced MerTK activation with receptor phosphorylation and signalling cascade, including non‐muscle myosin II redistribution and co‐localization with phagosomes. Tubby and Tulp1 are bridging molecules with their N‐terminal region as MerTK‐binding domain and C‐terminal region as phagocytosis prey‐binding domain (PPBD). Five minimal phagocytic determinants (MPDs) of K/R(X) 1–2 KKK in Tulp1 N‐terminus were defined as essential motifs for MerTK binding, receptor phosphorylation and phagocytosis. PPBD was mapped to the highly conserved 54 amino acids at the C‐terminal end of tubby and Tulp1. These data suggest that tubby and Tulp1 are novel bridging molecules to facilitate phagocytosis through MerTK.