title: The leucine-rich repeats of LINGO-1 are not required for self-interaction or interaction with the amyloid precursor protein.
abstract: LINGO-1 (leucine rich repeat and Ig domain containing Nogo receptor interacting protein-1) is a central nervous system transmembrane protein which simultaneously interacts with the Nogo-66 receptor and p75(NTR) or TROY on neurons to form a receptor complex responsible for myelin-mediated neurite outgrowth inhibition. On oligodendroglial cells, LINGO-1 interacts with p75(NTR) to constitutively inhibit multiple aspects of oligodendrocyte differentiation. Recently, LINGO-1 was identified as an in vivo interacting partner of the amyloid precursor protein (APP) and, correspondingly, cellular LINGO-1 expression was found to augment the release of the Abeta peptide, the potential causative agent of Alzheimer's disease. In addition, the recombinant LINGO-1 ectodomain has been shown to self-interact in solution and after crystallisation. Here, we have used deletional mutagenesis to identify the regions on LINGO-1 that are involved in homo- and heterotypic interactions. We have found that the N-terminal region containing the leucine-rich repeats along with the transmembrane and cytoplasmic domains of LINGO-1 are not required for self-interaction or interaction with APP.
authors: Autoimmunity, Transplantation and Inflammation Disease Area, Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors: Thomas
authors: T
authors: Stein
authors: Adrian Robert
authors: AR
authors: Walmsley
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D006801:Humans; D007930:Leucine / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; C482293:LINGO1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D007930:Leucine