title: Distinct 3-O-sulfated heparan sulfate modification patterns are required for kal-1-dependent neurite branching in a context-dependent manner in Caenorhabditis elegans.
abstract: Heparan sulfate (HS) is an unbranched glycosaminoglycan exhibiting substantial molecular diversity due to multiple, nonuniformly introduced modifications, including sulfations, epimerization, and acetylation. HS modifications serve specific and instructive roles in neuronal development, leading to the hypothesis of a HS code that regulates nervous system patterning. Although the in vivo roles of many of the HS modifications have been investigated, very little is known about the function of HS 3-O-sulfation in vivo. By examining patterning of the Caenorhabditis elegans nervous system in loss of function mutants of the two 3-O-sulfotransferases, hst-3.1 and hst-3.2, we found HS 3-O-sulfation to be largely dispensable for overall neural development. However, generation of stereotypical neurite branches in hermaphroditic-specific neurons required hst-3.1, hst-3.2, as well as an extracellular cell adhesion molecule encoded by kal-1, the homolog of Kallmann Syndrome associated gene 1/anosmin-1. In contrast, kal-1-dependent neurite branching in AIY neurons required catalytic activity of hst-3.2 but not hst-3.1. The context-dependent requirement for hst-3.2 and hst-3.1 indicates that both enzymes generate distinct types of HS modification patterns in different cell types, which regulate kal-1 to promote neurite branching. We conclude that HS 3-O-sulfation does not play a general role in establishing the HS code in C. elegans but rather plays a specialized role in a context-dependent manner to establish defined aspects of neuronal circuits.
authors: Department of Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors: Eillen
authors: E
authors: Tecle
authors: Carlos A
authors: CA
authors: Diaz-Balzac
authors: Hannes E
authors: HE
authors: Bülow
mesh_terms: D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002236:Carbohydrate Conformation; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D017238:Genes, Helminth; D017930:Genes, Reporter; D006497:Heparan Sulfate / Q000235:genetics / Q000378:metabolism*; D007814:Larva / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000201:enzymology*; D017354:Point Mutation; D034622:RNA Interference; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; D006497:Heparan Sulfate; D009419:Nerve Tissue Proteins; D015238:Sulfotransferases; C513487:KAL-1 protein, C elegans; C021350:heparitin sulfotransferase