Distinct 3-O-Sulfated Heparan Sulfate Modification Patterns Are Required for kal-1?Dependent Neurite Branching in a Context-Dependent Manner in Caenorhabditis elegans

摘要

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][1] and [hst-3.2][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][1] , [hst-3.2][2] , as well as an extracellular cell adhesion molecule encoded by [kal-1][3] , the homolog of Kallmann Syndrome associated gene 1/anosmin-1. In contrast, [kal-1][3] ?dependent neurite branching in AIY neurons required catalytic activity of [hst-3.2][2] but not [hst-3.1][1] . The context-dependent requirement for [hst-3.2][2] and [hst-3.1][1] indicates that both enzymes generate distinct types of HS modification patterns in different cell types, which regulate [kal-1][3] 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. [1]: http://www.wormbase.org/db/get?name=hst-3.1;class=Gene [2]: http://www.wormbase.org/db/get?name=hst-3.2;class=Gene [3]: http://www.wormbase.org/db/get?name=kal-1;class=Gene.