title: CRIM1 complexes with ß-catenin and cadherins, stabilizes cell-cell junctions and is critical for neural morphogenesis.
abstract: In multicellular organisms, morphogenesis is a highly coordinated process that requires dynamically regulated adhesion between cells. An excellent example of cellular morphogenesis is the formation of the neural tube from the flattened epithelium of the neural plate. Cysteine-rich motor neuron protein 1 (CRIM1) is a single-pass (type 1) transmembrane protein that is expressed in neural structures beginning at the neural plate stage. In the frog Xenopus laevis, loss of function studies using CRIM1 antisense morpholino oligonucleotides resulted in a failure of neural development. The CRIM1 knockdown phenotype was, in some cases, mild and resulted in perturbed neural fold morphogenesis. In severely affected embryos there was a dramatic failure of cell adhesion in the neural plate and complete absence of neural structures subsequently. Investigation of the mechanism of CRIM1 function revealed that it can form complexes with ß-catenin and cadherins, albeit indirectly, via the cytosolic domain. Consistent with this, CRIM1 knockdown resulted in diminished levels of cadherins and ß-catenin in junctional complexes in the neural plate. We conclude that CRIM1 is critical for cell-cell adhesion during neural development because it is required for the function of cadherin-dependent junctions.
authors.affiliation: The Visual Systems Group, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Virgilio G
authors.initials: VG
authors.lastname: Ponferrada
authors.forename: Jieqing
authors.initials: J
authors.lastname: Fan
authors.forename: Jefferson E
authors.initials: JE
authors.lastname: Vallance
authors.forename: Shengyong
authors.initials: S
authors.lastname: Hu
authors.forename: Aygun
authors.initials: A
authors.lastname: Mamedova
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rankin
authors.forename: Matthew
authors.initials: M
authors.lastname: Kofron
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Zorn
authors.forename: Rashmi S
authors.initials: RS
authors.lastname: Hegde
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lang
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D007365:Intercellular Junctions / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D009024:Morphogenesis / Q000502:physiology*; D060172:Morpholinos; D046912:Multiprotein Complexes / Q000378:metabolism*; D054259:Neural Tube / Q000196:embryology*; D029867:Xenopus Proteins / Q000378:metabolism* / Q000502:physiology; D014982:Xenopus laevis / Q000196:embryology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: C574374:CRIM1 protein, Xenopus; D015820:Cadherins; D017931:DNA Primers; D008565:Membrane Proteins; D060172:Morpholinos; D046912:Multiprotein Complexes; D029867:Xenopus Proteins; D051176:beta Catenin