PMID- 10629226
OWN - NLM
STAT- MEDLINE
DCOM- 20000309
LR  - 20191023
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 148
IP  - 1
DP  - 2000 Jan 10
TI  - Dual palmitoylation of PSD-95 mediates its vesiculotubular sorting, postsynaptic 
      targeting, and ion channel clustering.
PG  - 159-72
AB  - 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 NH(2) terminus. Mutations that
      disrupt dual palmitoylation of PSD-95 block both ion channel clustering by PSD-95
      and its synaptic targeting. Replacing the palmitoylated NH(2) terminus of PSD-95 
      with alternative palmitoylation motifs at either the NH(2) 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.
FAU - El-Husseini, A E
AU  - El-Husseini AE
AD  - Department of Physiology, University of California at San Francisco, San
      Francisco, California 94143, USA.
FAU - Craven, S E
AU  - Craven SE
FAU - Chetkovich, D M
AU  - Chetkovich DM
FAU - Firestein, B L
AU  - Firestein BL
FAU - Schnell, E
AU  - Schnell E
FAU - Aoki, C
AU  - Aoki C
FAU - Bredt, D S
AU  - Bredt DS
LA  - eng
GR  - R01-EY08055/EY/NEI NIH HHS/United States
GR  - R01-NS36017/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Dlg4 protein, rat)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (KCNA4 protein, human)
RN  - 0 (Kcna4 protein, rat)
RN  - 0 (Kv1.4 Potassium Channel)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Palmitic Acids)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (SAP90-PSD95 Associated Proteins)
RN  - 0 (postsynaptic density proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 20350-15-6 (Brefeldin A)
RN  - EC 2.7.4.4 (Nucleoside-Phosphate Kinase)
RN  - EC 2.7.4.8 (Guanylate Kinases)
RN  - SH1WY3R615 (Nocodazole)
SB  - IM
MH  - Animals
MH  - Biological Transport
MH  - Brefeldin A/pharmacology
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Cell Polarity
MH  - Cerebral Cortex/cytology
MH  - Consensus Sequence
MH  - Disks Large Homolog 4 Protein
MH  - Dogs
MH  - Epithelial Cells/metabolism
MH  - Green Fluorescent Proteins
MH  - Guanylate Kinases
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Kv1.4 Potassium Channel
MH  - Luminescent Proteins/genetics/metabolism
MH  - Membrane Proteins
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - Neurons/metabolism
MH  - Nocodazole/pharmacology
MH  - Nucleoside-Phosphate Kinase/metabolism
MH  - Palmitic Acids/*metabolism
MH  - Potassium Channels/*metabolism
MH  - *Potassium Channels, Voltage-Gated
MH  - Rats
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - SAP90-PSD95 Associated Proteins
MH  - Synapses
PMC - PMC2156213
EDAT- 2000/01/12 09:00
MHDA- 2000/03/11 09:00
CRDT- 2000/01/12 09:00
PHST- 2000/01/12 09:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 2000/01/12 09:00 [entrez]
AID - 10.1083/jcb.148.1.159 [doi]
PST - ppublish
SO  - J Cell Biol. 2000 Jan 10;148(1):159-72. doi: 10.1083/jcb.148.1.159.