Synaptogenesis Is Modulated by Heparan Sulfate in Caenorhabditis elegans

Genetics: A Periodical Record of Investigations Bearing on Heredity and Variation

article

María I. Lázaro-Peña¹  Carlos A. Díaz-Balzac¹  Hannes E. Bülow¹  Scott W. Emmons¹ 

[1] Department of Genetics, Albert Einstein College of Medicine, Bronx, New York 10461;Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461

关键词: C. elegans;    heparan sulfate;    neurexin;    neuroligin;    Proteoglycans;    synapse formation;   

DOI  :  10.1534/genetics.118.300837

学科分类：医学（综合）

来源: Genetics Society of America

【 摘 要 】

The nervous system regulates complex behaviors through a network of neurons interconnected by synapses. How specific synaptic connections are genetically determined is still unclear. Male mating is the most complex behavior in Caenorhabditis elegans . It is composed of sequential steps that are governed by > 3000 chemical connections. Here, we show that heparan sulfates (HS) play a role in the formation and function of the male neural network. HS, sulfated in position 3 by the HS modification enzyme HST-3.1 / HS 3- O -sulfotransferase and attached to the HS proteoglycan glypicans LON-2/glypican and GPN-1 /glypican, functions cell-autonomously and nonautonomously for response to hermaphrodite contact during mating. Loss of 3- O sulfation resulted in the presynaptic accumulation of RAB-3 , a molecule that localizes to synaptic vesicles, and disrupted the formation of synapses in a component of the mating circuits. We also show that the neural cell adhesion protein NRX-1 /neurexin promotes and the neural cell adhesion protein NLG-1 /neuroligin inhibits the formation of the same set of synapses in a parallel pathway. Thus, neural cell adhesion proteins and extracellular matrix components act together in the formation of synaptic connections.

【 授权许可】

CC BY