Complex cooperative functions of heparan sulfate proteoglycans shape nervous system development in Caenorhabditis elegans.
Bottom Line: Specifically, lon-2/glypican and unc-52/perlecan act in parallel genetic pathways and display synergistic interactions with sdn-1/syndecan to mediate kal-1 function.Because all of these heparan sulfate core proteins have been shown to act in different tissues, these studies indicate that KAL-1/anosmin-1 requires heparan sulfate with distinct modification patterns of different cellular origin for function.Our results support a model in which a three-dimensional scaffold of heparan sulfate mediates KAL-1/anosmin-1 and intercellular communication through complex and cooperative interactions.
Affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, 10461.Show MeSH
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Mentions: A possible role of the polyanionic HS could be to bind and localize KAL-1 to the cell surface. Alternatively, specific HS modification patterns could modulate KAL-1 function by determining possible interactions with other factors. To distinguish between these possibilities, we analyzed the localization of KAL-1 expression in different backgrounds mutant for HS-modifying enzymes. In animals in which KAL-1 is misexpressed in AIY neurons, KAL-1 appears localized to the cellular periphery (Figure 5) (Bülow et al. 2002). We found the localization of KAL-1 to not be visibly different in any of the mutants, including hse-5, hst-2, hst-6, or hst-3.2 (Figure 5). Because most mutants individually completely suppress the kal-1-dependent branching phenotype in AIY neurons, these data suggest that the major function of HS is not to retain and localize KAL-1 to the cell surface, but rather suggest that HS may be required to mediate how KAL-1 interacts with other factors.
Affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, 10461.