title: The secreted immunoglobulin domain proteins ZIG-5 and ZIG-8 cooperate with L1CAM/SAX-7 to maintain nervous system integrity.
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.
authors: Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America. Claire.Benard@umassmed.edu
authors: Claire Y
authors: CY
authors: Bénard
authors: Cassandra
authors: C
authors: Blanchette
authors: Janine
authors: J
authors: Recio
authors: Oliver
authors: O
authors: Hobert
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics; D009420:Nervous System / Q000254:growth & development* / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D007136:Immunoglobulins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D020033:Protein Isoforms; C501528:SAX-7 protein, C elegans; D029961:Zebrafish Proteins; C577067:Zig-5 protein, C elegans; C577068:Zig-8 protein, C elegans