Advanced

{gamma}-Secretase and metalloproteinase activity regulate the distribution of endoplasmic reticulum to hippocampal neuron dendritic spines.

Ng, Ai Na LU and Toresson, Håkan LU (2008) In FASEB Journal 22(8). p.2832-2842
Abstract
The neuronal endoplasmic reticulum (ER) contributes to many physiological and pathological processes in the brain. A subset of dendritic spines on hippocampal neurons contains ER that may contribute to synapse-specific intracellular signaling. Distribution of ER to spines is dynamic, but knowledge of the regulatory mechanisms is lacking. In live cell imaging experiments we now show that cultured hippocampal neurons rapidly lost ER from spines after phorbol ester treatment. ER loss was reduced by inhibiting gamma-secretase (DAPT at 2 microM) and metalloproteinase (TAPI-0 and GM6001 at 4 microM) activity. Inhibition of protein kinase C also diminished loss of ER by preventing exit of ER from spines. Furthermore, gamma-secretase and... (More)
The neuronal endoplasmic reticulum (ER) contributes to many physiological and pathological processes in the brain. A subset of dendritic spines on hippocampal neurons contains ER that may contribute to synapse-specific intracellular signaling. Distribution of ER to spines is dynamic, but knowledge of the regulatory mechanisms is lacking. In live cell imaging experiments we now show that cultured hippocampal neurons rapidly lost ER from spines after phorbol ester treatment. ER loss was reduced by inhibiting gamma-secretase (DAPT at 2 microM) and metalloproteinase (TAPI-0 and GM6001 at 4 microM) activity. Inhibition of protein kinase C also diminished loss of ER by preventing exit of ER from spines. Furthermore, gamma-secretase and metalloproteinase inhibition, in the absence of phorbol ester, triggered a dramatic increase in spine ER content. Metalloproteinases and gamma-secretase cleave several transmembrane proteins. Many of these substrates are known to localize to adherens junctions, a structural specialization with which spine ER interacts. One interesting possibility is thus that ER content within spines may be regulated by proteolytic activity affecting adherens junctions. Our data demonstrate a hitherto unknown role for these two proteolytic activities in regulating dynamic aspects of cellular ultrastructure, which is potentially important for cellular calcium homeostasis and several intracellular signaling pathways.-Ng, A. N., Toresson, H. gamma-Secretase and metalloproteinase activity regulate the distribution of endoplasmic reticulum to hippocampal neuron dendritic spines. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
primary culture, synapse, live cell imaging
in
FASEB Journal
volume
22
issue
8
pages
2832 - 2842
publisher
The Federation of American Societies for Experimental Biology
external identifiers
  • wos:000258089300023
  • pmid:18424769
  • scopus:48749085962
ISSN
1530-6860
DOI
10.1096/fj.07-103903
language
English
LU publication?
yes
id
e95b6ac1-5cd4-4b2e-aa7e-3244a68d4535 (old id 1147219)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18424769?dopt=Abstract
date added to LUP
2008-05-06 14:34:00
date last changed
2017-01-01 05:54:27
@article{e95b6ac1-5cd4-4b2e-aa7e-3244a68d4535,
  abstract     = {The neuronal endoplasmic reticulum (ER) contributes to many physiological and pathological processes in the brain. A subset of dendritic spines on hippocampal neurons contains ER that may contribute to synapse-specific intracellular signaling. Distribution of ER to spines is dynamic, but knowledge of the regulatory mechanisms is lacking. In live cell imaging experiments we now show that cultured hippocampal neurons rapidly lost ER from spines after phorbol ester treatment. ER loss was reduced by inhibiting gamma-secretase (DAPT at 2 microM) and metalloproteinase (TAPI-0 and GM6001 at 4 microM) activity. Inhibition of protein kinase C also diminished loss of ER by preventing exit of ER from spines. Furthermore, gamma-secretase and metalloproteinase inhibition, in the absence of phorbol ester, triggered a dramatic increase in spine ER content. Metalloproteinases and gamma-secretase cleave several transmembrane proteins. Many of these substrates are known to localize to adherens junctions, a structural specialization with which spine ER interacts. One interesting possibility is thus that ER content within spines may be regulated by proteolytic activity affecting adherens junctions. Our data demonstrate a hitherto unknown role for these two proteolytic activities in regulating dynamic aspects of cellular ultrastructure, which is potentially important for cellular calcium homeostasis and several intracellular signaling pathways.-Ng, A. N., Toresson, H. gamma-Secretase and metalloproteinase activity regulate the distribution of endoplasmic reticulum to hippocampal neuron dendritic spines.},
  author       = {Ng, Ai Na and Toresson, Håkan},
  issn         = {1530-6860},
  keyword      = {primary culture,synapse,live cell imaging},
  language     = {eng},
  number       = {8},
  pages        = {2832--2842},
  publisher    = {The Federation of American Societies for Experimental Biology},
  series       = {FASEB Journal},
  title        = {{gamma}-Secretase and metalloproteinase activity regulate the distribution of endoplasmic reticulum to hippocampal neuron dendritic spines.},
  url          = {http://dx.doi.org/10.1096/fj.07-103903},
  volume       = {22},
  year         = {2008},
}