Synaptogenesis Is Modulated by Heparan Sulfate in Caenorhabditis elegans
Synaptogenesis Is Modulated by Heparan Sulfate in Caenorhabditis elegans
复制标题
DOI：
10.1534/genetics.118.300837
复制
发表时间：
2018-05-01
期刊：
影响因子：
3.3
通讯作者：
Emmons, Scott W.
中科院分区：
文献类型：
--
作者：
Lazaro-Pena, Maria I.;Diaz-Balzac, Carlos A.;Emmons, Scott W.
神经系统通过由突触互连的神经元网络来调节复杂的行为。具体的突触连接是如何由基因决定的，目前还不清楚。雄性交配是秀丽隐杆线虫最复杂的行为。它由超过3000个化学连接决定的顺序步骤组成。在这里，我们表明硫酸乙酰肝素（HS）在男性神经网络的形成和功能中发挥作用。HS在3位被HS修饰酶HST-3.1/HS 3-O-磺基转移酶硫酸化，并与HS蛋白聚糖磷脂酰肌醇蛋白聚糖LON-2/磷脂酰肌醇蛋白聚糖和GPN-1/磷脂酰肌醇蛋白聚糖连接，在交配期间对雌雄同体接触的反应中发挥细胞自主和非自主的功能。3-O硫酸化的丧失导致RAB-3的突触前积累，RAB-3是一种定位于突触囊泡的分子，并破坏了交配回路组件中突触的形成。我们还表明，神经细胞粘附蛋白NRX-1/neurexin促进和神经细胞粘附蛋白NLG-1/neuroligin抑制形成相同的突触在一个平行的途径。因此，神经细胞粘附蛋白和细胞外基质成分在突触连接的形成中共同起作用。
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.