|
  
- 积分
- 0
- 威望
- 0
- 包包
- 3465
|
Bredt/Elsevier
2 I* Z$ z7 o+ [# [% y( `
7 r% V t' ]- `Learning is probably driven by use-dependent changes in synaptic strength. Now, Alaa El-Husseini, David Bredt (University of California at San Francisco, San Francisco, CA), and colleagues have identified regulated protein palmitoylation as one means to control the strength of synapse responses.Synaptic activity is controlled by AMPA channels, which respond to the neurotransmitter glutamate by letting in Na until the neuron fires. Ca2 influx through NMDA receptors (also activated by glutamate) alters synaptic responses by influencing the number of AMPA receptors clustered at the synapse.! V% U. I& s0 y8 v! ?, h. D+ l) q
& Q5 K. `. u$ |) dIt now appears that protein palmitoylation is key to this modulation. The localization of AMPA receptors is controlled by the PDZ domain protein PSD-95, which also clusters at synapses and binds to the AMPA-trafficking protein stargazin. The clustering of PSD-95 is known to require its palmitoylation. Now, Bredt and colleagues demonstrate that increased glutamate receptor activity accelerates depalmitoylation of PSD-95 and that depalmitoylation causes endocytosis and dispersion of both PSD-95 and AMPA receptors, leading to depression of synaptic strength.
* k# k3 n+ {4 F$ t. w x
; X8 _5 e6 z8 V0 p! P- M"This defines a mechanism for activity-dependent changes in AMPA receptor numbers and defines protein palmitoylation as a new signaling mechanism at synapses," says Bredt. The enzymes that add and remove PSD-95 palmitoyl groups have not been identified, but Bredt speculates that they will be Ca2 regulated, as Ca2 entry into the cell (e.g., through NMDA receptors) is required for AMPA dispersion.% \+ ], m x, B) p8 @& Q7 x
1 f, H# N- ^- Z- P- w0 ^( A& G
Reference:
4 t& n: T) S+ Z3 s! y6 i- o! {7 }7 n% p3 f) M. o/ P- t
El-Husseini, A., et al. 2002. Cell. 108:849–863.(Clusters of AMPA receptors (red spots) d) |
|
发表于 2009-3-6 00:07
发表于 2015-6-10 09:35
