JCB logo
amgmicro.com
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 984K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by El-Husseini, A. E.
Right arrow Articles by Bredt, D. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by El-Husseini, A. E.
Right arrow Articles by Bredt, D. S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

© The Rockefeller University Press, 0021-9525/2000//159 $5.00
The Journal of Cell Biology, Volume 148, Number 1, , 2000 159-172

Original Article

Dual Palmitoylation of Psd-95 Mediates Its Vesiculotubular Sorting, Postsynaptic Targeting, and Ion Channel Clustering



Alaa E. El-Husseinia, Sarah E. Cravena, Dane M. Chetkovicha,b, Bonnie L. Firesteina, Eric Schnella, Chiye Aokic, and David S. Bredta

a Department of Physiology, University of California at San Francisco, San Francisco, California 94143
b Department of Neurology, University of California at San Francisco, San Francisco, California 94143
c Center for Neural Science, New York University, New York 10003
University of California at San Francisco School of Medicine, 513 Parnassus Ave., San Francisco, CA 94143-0444.(415) 476-4929(415) 476-6310

bredt{at}itsa.ucsf.edu

Postsynaptic density-95 (PSD-95/SAP-90) is a palmitoylated peripheral membrane protein that scaffolds ion channels at excitatory synapses. To elucidate mechanisms for postsynaptic ion channel clustering, we analyzed the cellular trafficking of PSD-95. We find that PSD-95 transiently associates with a perinuclear membranous compartment and traffics with vesiculotubular structures, which migrate in a microtubule-dependent manner. Trafficking of PSD-95 with these vesiculotubular structures requires dual palmitoylation, which is specified by five consecutive hydrophobic residues at the NH2 terminus. Mutations that disrupt dual palmitoylation of PSD-95 block both ion channel clustering by PSD-95 and its synaptic targeting. Replacing the palmitoylated NH2 terminus of PSD-95 with alternative palmitoylation motifs at either the NH2 or COOH termini restores ion channel clustering also induces postsynaptic targeting, respectively. In brain, we find that PSD-95 occurs not only at PSDs but also in association with intracellular smooth tubular structures in dendrites and spines. These data imply that PSD-95 is an itinerant vesicular protein; initial targeting of PSD-95 to an intracellular membrane compartment may participate in postsynaptic ion channel clustering by PSD-95.

Key Words: PSD • palmitoylation • trafficking • MAGUK • clustering

© 2000 The Rockefeller University Press

The online version of this article contains supplemental material.

Abbreviations used in this paper: BFA, brefeldin A; dlg, discs large; GAP-43, growth associated protein-43; GFP, green fluorescent protein; MAGUK, membrane-associated guanylate kinase; NMDA, N-methyl-D-aspartate; PDZ, postsynaptic density-95, discs large, zonula occludens; PSD, postsynaptic density.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents