Remodeling of the postsynaptic plasma membrane during neural development

被引:83
|
作者
Tulodziecka, Karolina [1 ]
Diaz-Rohrer, Barbara B. [1 ]
Farley, Madeline M. [2 ]
Chan, Robin B. [3 ]
Di Paolo, Gilbert [3 ,4 ]
Levental, Kandice R. [1 ]
Waxham, M. Neal [2 ]
Levental, Ilya [1 ]
机构
[1] Univ Texas Hlth Sci Ctr Houston, Dept Integrat Biol & Pharmacol, McGovern Med Sch, Houston, TX 77030 USA
[2] Univ Texas Hlth Sci Ctr Houston, Dept Neurobiol & Anat, McGovern Med Sch, Houston, TX 77030 USA
[3] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA
[4] Denali Therapeut, San Francisco, CA 94080 USA
基金
美国国家卫生研究院;
关键词
ION-CHANNEL FUNCTION; DOCOSAHEXAENOIC ACID; LIPID-COMPOSITION; QUANTITATIVE-ANALYSIS; EPITHELIAL-CELLS; APICAL MEMBRANE; RAT-BRAIN; RAFT; VESICLES; DOMAINS;
D O I
10.1091/mbc.E16-06-0420
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:3480 / 3489
页数:10
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