title: The intracellular domain of teneurin-1 interacts with MBD1 and CAP/ponsin resulting in subcellular codistribution and translocation to the nuclear matrix.
abstract: Teneurin-1 is a type II transmembrane protein expressed in neurons of the developing and adult central nervous system. To investigate the intracellular signaling of teneurin-1, we searched for proteins interacting with its intracellular domain. One of the proteins identified is the c-Cbl-associated protein CAP/ponsin, an adaptor protein containing SH3 domains. This interaction results on one hand in the recruitment of the soluble intracellular domain of teneurin-1 to the cell membrane enriched in CAP/ponsin. On the other hand, it leads to the translocation of CAP/ponsin to the nucleus, the major site of accumulation of the intracellular domain of teneurin-1. The second interacting protein identified is the methyl-CpG binding protein MBD1. In the nucleus, the intracellular domain of teneurin-1 colocalizes with this transcriptional repressor in foci associated with the nuclear matrix. We propose that these interactions are part of a specific signaling pathway. Evidence for cleavage and nuclear translocation of the intracellular domain has been obtained by the detection of endogenous teneurin-1 immunoreactivity in nuclear speckles in chick embryo fibroblasts. Furthermore, in the nuclear matrix fraction of these cells as well as in cells expressing a hormone-inducible full-length teneurin-1 protein, a teneurin-1 fragment of identical size could be detected as in cells transfected with the intracellular domain alone.
authors.affiliation: Friedrich Miescher Institute, Novartis Research Foundation, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Nunes
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Ferralli
authors.forename: Karen
authors.initials: K
authors.lastname: Choi
authors.forename: Marianne
authors.initials: M
authors.lastname: Brown-Luedi
authors.forename: Ariane D
authors.initials: AD
authors.lastname: Minet
authors.forename: Ruth
authors.initials: R
authors.lastname: Chiquet-Ehrismann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D015530:Nuclear Matrix / Q000378:metabolism*; D021381:Protein Transport; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000378:metabolism; D019063:Tenascin / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; C066141:MBD1 protein, human; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D019063:Tenascin; D014157:Transcription Factors; C119201:ponsin; C120530:teneurin-1