Faculty Collaboration Database

Distinct 3-O-sulfated heparan sulfate modification patterns are required for kal-1-dependent neurite branching in a context-dependent manner in Caenorhabditis elegans. G3 (Bethesda) 2013 Mar;3(3):541-52

Date

03/02/2013

Pubmed ID

23451335

Pubmed Central ID

PMC3583460

DOI

10.1534/g3.112.005199

Scopus ID

2-s2.0-84883234314 (requires institutional sign-in at Scopus site)   32 Citations

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.

Author List

Tecle E, Diaz-Balzac CA, Bülow HE

Author

Eillen Tecle PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Alleles
Animals
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Carbohydrate Conformation
Enzyme Activation
Gene Expression Regulation, Enzymologic
Genes, Helminth
Genes, Reporter
Heparitin Sulfate
Larva
Nerve Tissue Proteins
Neurites
Point Mutation
RNA Interference
Sulfotransferases
Transcription, Genetic