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LIM‐only protein 4 interacts directly with the repulsive guidance molecule A receptor Neogenin
Author(s) -
Schaffar Gregor,
Taniguchi Junko,
Brodbeck Tanja,
Meyer Axel H.,
Schmidt Martin,
Yamashita Toshihide,
Mueller Bernhard K.
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05621.x
Subject(s) - receptor , microbiology and biotechnology , chemistry , biophysics , biology , biochemistry
Repulsive guidance molecule A (RGM A) was recently described as a potent inhibitor of neuroregeneration in a rat spinal cord injury model. The receptor mediating RGM A’s repulsive activity was shown to be Neogenin, a member of the Deleted in Colorectal Cancer (DCC) family of netrin receptors. Binding of RGM A to Neogenin induces activation of the small GTPase RhoA and of its effector Rho‐kinase by an unknown mechanism. Here we show, that the cytoplasmic tail of Neogenin interacts directly with the transcriptional coactivator LIM domain only 4 (LMO4) in human SH‐SY5Y cells, human Ntera neurons, and in embryonic rat cortical neurons. RGM A binding to Neogenin but not binding of Netrin‐1, induces release of LMO4 from Neogenin. Down‐regulation of LMO4 neutralizes the repulsive activity of RGM A in neuronal cell lines and embryonic rat cortical neurons and prevents RhoA activation. These results show for the first time that an interaction of Neogenin with LMO4 is involved in the RGM A – Neogenin signal transduction pathway for RhoA activation.