Sphingolipids regulate neuromuscular synapse structure and function in Drosophila.
Sphingolipids regulate neuromuscular synapse structure and function in Drosophila.
复制标题
DOI：
10.1002/cne.24466
复制
发表时间：
2018-09-01
期刊：
影响因子：
--
通讯作者：
Sweeney ST
中科院分区：
文献类型：
--
作者：
West RJH;Briggs L;Perona Fjeldstad M;Ribchester RR;Sweeney ST
在突触中发现大量的鞘磷脂，并与突触结构、功能和变性的调节有关。然而，它们在这些过程中的确切作用仍然不清楚。丝氨酸棕榈酰基转移酶(SPT)是合成鞘磷脂的第一步酶促反应。对果蝇幼虫神经肌肉接头(NMJ)的分析表明，SPT酶亚基Lace/SPTLC2的突变导致突触结构和功能的缺陷。虽然NMJ长度在蕾丝突变体中是正常的，但每个NMJ的外显子数量减少到野生型数量的∼的50%。花边突变体的突触突起要大得多，但对一般超微结构几乎没有影响。对突触的电生理学分析表明，突触传递很强，并且以抑制为主，而不是促进。蕾丝的结构和功能表型反映了basigin(BSG)的一些方面，basigin是一种小的Ig结构域黏附分子，也被认为调节突触结构和功能。Lace和BSG的突变组合产生了大的突触突触，而Lace突变体则显示BSG在突触处异常聚集，这表明BSG需要神经鞘磷脂来调节突触的结构。为了支持这一点，我们发现BSG富含脂筏。我们的数据表明，鞘脂在突触结构和功能的调节和微调中起作用，而鞘脂对突触结构的调节可能是通过BSG的活性来介导的。
Sphingolipids are found in abundance at synapses and have been implicated in regulation of synapse structure, function, and degeneration. Their precise role in these processes, however, remains obscure. Serine Palmitoyl‐transferase (SPT) is the first enzymatic step for synthesis of sphingolipids. Analysis of the Drosophila larval neuromuscular junction (NMJ) revealed mutations in the SPT enzyme subunit, lace/SPTLC2 resulted in deficits in synaptic structure and function. Although NMJ length is normal in lace mutants, the number of boutons per NMJ is reduced to ∼50% of the wild type number. Synaptic boutons in lace mutants are much larger but show little perturbation to the general ultrastructure. Electrophysiological analysis of lace mutant synapses revealed strong synaptic transmission coupled with predominance of depression over facilitation. The structural and functional phenotypes of lace mirrored aspects of Basigin (Bsg), a small Ig‐domain adhesion molecule also known to regulate synaptic structure and function. Mutant combinations of lace and Bsg generated large synaptic boutons, while lace mutants showed abnormal accumulation of Bsg at synapses, suggesting that Bsg requires sphingolipid to regulate structure of the synapse. In support of this, we found Bsg to be enriched in lipid rafts. Our data points to a role for sphingolipids in the regulation and fine‐tuning of synaptic structure and function while sphingolipid regulation of synaptic structure may be mediated via the activity of Bsg.
登录
查看更多内容
影响因子：
16.2
作者：
Koh, TW;Verstreken, P;Bellen, HJ
通讯作者：
Bellen, HJ
影响因子：
5.5
作者：
DODGE, FA;RAHAMIMO.R
通讯作者：
RAHAMIMO.R
DOI：
10.1073/pnas.0607721104
发表时间：
2007-04-17
影响因子：
11.1
作者：
Krebs, Stefan;Medugorac, Ivica;Foerster, Martin
通讯作者：
Foerster, Martin
影响因子：
12.4
作者：
Ciarlo, L.;Manganelli, V.;Sorice, M.
通讯作者：
Sorice, M.
DOI：
10.1073/pnas.091502398
发表时间：
2001-05-08
影响因子：
11.1
作者：
Chamberlain, LH;Burgoyne, RD;Gould, GW
通讯作者：
Gould, GW