期刊
MOLECULAR BIOLOGY OF THE CELL
卷 27, 期 22, 页码 3480-3489出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E16-06-0420
关键词
-
类别
资金
- National Institutes of Health [R01 NS056049]
- Cancer Prevention and Research Institute of Texas [R1215]
- National Institute of General Medical Sciences, National Institutes of Health [1R01GM114282]
- UT BRAIN Seed Program [362640]
- Ruth Kirschstein NRSA award from the National Institutes of Health/National Institute of Neurological Disorders and Stroke [F31NS084671]
Neuronal synapses are the fundamental units of neural signal transduction and must maintain exquisite signal fidelity while also accommodating the plasticity that underlies learning and development. To achieve these goals, the molecular composition and spatial organization of synaptic terminals must be tightly regulated; however, little is known about the regulation of lipid composition and organization in synaptic membranes. Here we quantify the comprehensive lipidome of rat synaptic membranes during postnatal development and observe dramatic developmental lipidomic remodeling during the first 60 postnatal days, including progressive accumulation of cholesterol, plasmalogens, and sphingolipids. Further analysis of membranes associated with isolated postsynaptic densities (PSDs) suggests the PSD-associated postsynaptic plasma membrane (PSD-PM) as one specific location of synaptic remodeling. We analyze the biophysical consequences of developmental remodeling in reconstituted synaptic membranes and observe remarkably stable microdomains, with the stability of domains increasing with developmental age. We rationalize the developmental accumulation of microdomain-forming lipids in synapses by proposing a mechanism by which palmitoylation of the immobilized scaffold protein PSD-95 nucleates domains at the postsynaptic plasma membrane. These results reveal developmental changes in lipid composition and palmitoylation that facilitate the formation of postsynaptic membrane microdomains, which may serve key roles in the function of the neuronal synapse.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据