title: Protracted and asynchronous accumulation of PSD95-family MAGUKs during maturation of nascent dendritic spines.
abstract: The formation and stabilization of new dendritic spines is a key component of the experience-dependent neural circuit plasticity that supports learning, but the molecular maturation of nascent spines remains largely unexplored. The PSD95-family of membrane-associated guanylate kinases (PSD-MAGUKs), most notably PSD95, has a demonstrated role in promoting spine stability. However, nascent spines contain low levels of PSD95, suggesting that other members of the PSD-MAGUK family might act to stabilize nascent spines in the early stages of spiny synapse formation. Here, we used GFP-fusion constructs to quantitatively define the molecular composition of new spines, focusing on the PSD-MAGUK family. We found that PSD95 levels in new spines were as low as those previously associated with rapid subsequent spine elimination, and new spines did not achieve mature levels of PSD95 until between 12 and 20 h following new spine identification. Surprisingly, we found that the PSD-MAGUKs PSD93, SAP97, and SAP102 were also substantially less enriched in new spines. However, they accumulated in new spines more quickly than PSD95: SAP102 enriched to mature levels within 3 h, SAP97 and PSD93 enriched gradually over the course of 6 h. Intriguingly, when we restricted our analysis to only those new spines that persisted, SAP97 was the only PSD-MAGUK already present at mature levels in persistent new spines when first identified. Our findings uncover a key structural difference between nascent and mature spines, and suggest a mechanism for the stabilization of nascent spines through the sequential arrival of PSD-MAGUKs. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1161-1174, 2017.
authors.affiliation: Center for Neuroscience, University of California Davis, Davis, California, 95618.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Lambert
authors.affiliation: Center for Neuroscience, University of California Davis, Davis, California, 95618.
authors.forename: Travis C
authors.initials: TC
authors.lastname: Hill
authors.affiliation: Center for Neuroscience, University of California Davis, Davis, California, 95618.
authors.forename: Deborah K
authors.initials: DK
authors.lastname: Park
authors.affiliation: Center for Neuroscience, University of California Davis, Davis, California, 95618.
authors.forename: Julie H
authors.initials: JH
authors.lastname: Culp
authors.affiliation: Center for Neuroscience, University of California Davis, Davis, California, 95618.
authors.forename: Karen
authors.identifier: 0000-0002-0799-0460
authors.initials: K
authors.lastname: Zito
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D049229:Dendritic Spines / Q000201:enzymology*; D005260:Female; D049452:Green Fluorescent Proteins; D051528:Guanylate Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D017966:Pyramidal Cells / Q000201:enzymology; D051381:Rats; D046509:Tissue Culture Techniques; D000099273:Neurabins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D049452:Green Fluorescent Proteins; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D000099273:Neurabins; C501119:Dlg1 protein, rat; C101195:Dlg3 protein, rat; C501451:Mpp2 protein, rat
keywords: 2-photon imaging; PSD-MAGUK; dendritic spine; hippocampus; structural plasticity