The Secreted Immunoglobulin Domain Proteins ZIG-5 and ZIG-8 Cooperate with L1CAM/SAX-7 to Maintain Nervous System Integrity
Student Authors
Cassandra BlanchetteAcademic Program
NeuroscienceUMass Chan Affiliations
Graduate School of Biomedical Sciences, Neuroscience ProgramBenard Lab
Neurobiology
Document Type
Journal ArticlePublication Date
2012-07-19Keywords
Immunoglobulins; Neural Cell Adhesion Molecule L1; Neural Cell Adhesion MoleculesNeuroscience and Neurobiology
Metadata
Show full item recordAbstract
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.1002819Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33251PubMed ID
22829780Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1371/journal.pgen.1002819