title: Remodeling of the postsynaptic plasma membrane during neural development.
abstract: 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.
authors.affiliation: Department of Integrative Biology and Pharmacology, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX 77030.
authors.forename: Karolina
authors.initials: K
authors.lastname: Tulodziecka
authors.affiliation: Department of Integrative Biology and Pharmacology, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX 77030.
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Diaz-Rohrer
authors.affiliation: Department of Neurobiology and Anatomy, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX 77030.
authors.forename: Madeline M
authors.initials: MM
authors.lastname: Farley
authors.affiliation: Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032.
authors.forename: Robin B
authors.initials: RB
authors.lastname: Chan
authors.affiliation: Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Di Paolo
authors.affiliation: Department of Integrative Biology and Pharmacology, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX 77030.
authors.forename: Kandice R
authors.initials: KR
authors.lastname: Levental
authors.affiliation: Department of Neurobiology and Anatomy, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX 77030 ilya.levental@uth.tmc.edu M.N.Waxham@uth.tmc.edu.
authors.forename: M Neal
authors.initials: MN
authors.lastname: Waxham
authors.affiliation: Department of Integrative Biology and Pharmacology, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX 77030 ilya.levental@uth.tmc.edu M.N.Waxham@uth.tmc.edu.
authors.forename: Ilya
authors.initials: I
authors.lastname: Levental
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D008055:Lipids; D054878:Lipoylation; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis; D009473:Neuronal Plasticity; D057907:Post-Synaptic Density / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D013570:Synaptic Membranes / Q000378:metabolism
chemical_list: D008055:Lipids; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins