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    The Secreted Immunoglobulin Domain Proteins ZIG-5 and ZIG-8 Cooperate with L1CAM/SAX-7 to Maintain Nervous System Integrity

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    Authors
    Benard, Claire Y.
    Blanchette, Cassandra
    Recio, Janine
    Hobert, Oliver
    Student Authors
    Cassandra Blanchette
    Academic Program
    Neuroscience
    UMass Chan Affiliations
    Graduate School of Biomedical Sciences, Neuroscience Program
    Benard Lab
    Neurobiology
    Document Type
    Journal Article
    Publication Date
    2012-07-19
    Keywords
    Immunoglobulins; Neural Cell Adhesion Molecule L1; Neural Cell Adhesion Molecules
    Neuroscience and Neurobiology
    
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    Abstract
    During nervous system development, neuronal cell bodies and their axodendritic projections are precisely positioned through transiently expressed patterning cues. We show here that two neuronally expressed, secreted immunoglobulin (Ig) domain-containing proteins, ZIG-5 and ZIG-8, have no detectable role during embryonic nervous system development of the nematode Caenorhabditis elegans but are jointly required for neuronal soma and ventral cord axons to maintain their correct position throughout postembryonic life of the animal. The maintenance defects observed upon removal of zig-5 and zig-8 are similar to those observed upon complete loss of the SAX-7 protein, the C. elegans ortholog of the L1CAM family of adhesion proteins, which have been implicated in several neurological diseases. SAX-7 exists in two isoforms: a canonical, long isoform (SAX-7L) and a more adhesive shorter isoform lacking the first two Ig domains (SAX-7S). Unexpectedly, the normally essential function of ZIG-5 and ZIG-8 in maintaining neuronal soma and axon position is completely suppressed by genetic removal of the long SAX-7L isoform. Overexpression of the short isoform SAX-7S also abrogates the need for ZIG-5 and ZIG-8. Conversely, overexpression of the long isoform disrupts adhesion, irrespective of the presence of the ZIG proteins. These findings suggest an unexpected interdependency of distinct Ig domain proteins, with one isoform of SAX-7, SAX-7L, inhibiting the function of the most adhesive isoform, SAX-7S, and this inhibition being relieved by ZIG-5 and ZIG-8. Apart from extending our understanding of dedicated neuronal maintenance mechanisms, these findings provide novel insights into adhesive and anti-adhesive functions of IgCAM proteins.
    Source

    Bénard CY, Blanchette C, Recio J, Hobert O (2012) The Secreted Immunoglobulin Domain Proteins ZIG-5 and ZIG-8 Cooperate with L1CAM/SAX-7 to Maintain Nervous System Integrity. PLoS Genet 8(7): e1002819. doi:10.1371/journal.pgen.1002819. Link to article on publisher's site

    DOI
    10.1371/journal.pgen.1002819
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/33251
    PubMed ID
    22829780
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.pgen.1002819
    Scopus Count
    Collections
    Morningside GSBS Scholarly Publications
    Neurobiology Student Publications
    Neurobiology Faculty Publications

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