HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 45, 44393-44399, November 7, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/45/44393    most recent M300971200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ris, L. Articles by Van Leuven, F. Search for Related Content PubMed PubMed Citation Articles by Ris, L. Articles by Van Leuven, F. Social Bookmarking                      What's this?

Capacitative Calcium Entry Induces Hippocampal Long Term Potentiation in the Absence of Presenilin-1^*

Laurence Ris, Ilse Dewachter¶||, Delphine Reversé, Emile Godaux**, and Fred Van Leuven¶

From the Laboratory of Neuroscience, University of Mons-Hainaut, B-7000 Mons and the ^¶Experimental Genetics Group, Department of Human Genetics, KULeuven, B-3000 Leuven, Belgium

Presenilins, whose mutant forms are the most common cause of early onset familial Alzheimer's disease, are involved in two very distinct processes: (i) proteolytic activity as -secretase acting on amyloid precursor protein to produce amyloid peptides and (ii) storage of Ca²⁺ in the endoplasmic reticulum (ER). In particular, absence of presenilin-1 (PS1) was claimed to potentiate capacitative calcium entry (CCE), i.e. the mechanism of replenishment of ER Ca²⁺ stores. However, until now, evidence in favor of the latter role has been obtained only in isolated or cultured cells and not on neurons in situ. Here, we studied the strength of the synapses between Schaffer's collaterals and CA1 neurons in hippocampal slices when they were submitted first to Ca²⁺-free medium containing thapsigargin and subsequently to normal artificial cerebrospinal fluid, a procedure known to trigger CCE. We demonstrate that Ca²⁺ influx via the CCE mechanism is sufficient to trigger robust long term potentiation of the synapses in hippocampal slices from transgenic mice with a postnatal, neuron-specific ablation of PS1, but remarkably not from wild-type mice. Our data establish for the first time in neurons confined in normal neuronal networks that PS1 acts on the refilling mechanism of ER Ca²⁺ stores.

Received for publication, January 29, 2003 , and in revised form, July 21, 2003.

^* This investigation was supported by the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, by European Economic Community (EEC)-Biotech, by EEC-5FP, by the Rooms-fund, by KULeuven Research Fund, by KULeuven R&D, by the Queen Elisabeth Fund for Medical Research, and by the Belgian National Fund for Scientific Medical Research. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Scientific Research Worker of the Belgian National Fund for Scientific Research.

^|| Postdoctoral fellow of FWO-Vlaanderen.

^** To whom correspondence should be addressed: University of Mons-Hainaut, Laboratory of Neuroscience, Place du Parc, 20, B-7000 Mons, Belgium. Tel.: 32-65-373570; Fax: 32-65-373573; E-mail: emile.godaux{at}umh.ac.be.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. N. Ng and H. Toresson {gamma}-Secretase and metalloproteinase activity regulate the distribution of endoplasmic reticulum to hippocampal neuron dendritic spines FASEB J, August 1, 2008; 22(8): 2832 - 2842. [Abstract] [Full Text] [PDF]

				B. A. Kachoei, R. J. Knox, D. Uthuza, S. Levy, L. K. Kaczmarek, and N. S. Magoski A Store-Operated Ca2+ Influx Pathway in the Bag Cell Neurons of Aplysia J Neurophysiol, November 1, 2006; 96(5): 2688 - 2698. [Abstract] [Full Text] [PDF]

				D. Terwel, R. Lasrado, J. Snauwaert, E. Vandeweert, C. Van Haesendonck, P. Borghgraef, and F. Van Leuven Changed Conformation of Mutant Tau-P301L Underlies the Moribund Tauopathy, Absent in Progressive, Nonlethal Axonopathy of Tau-4R/2N Transgenic Mice J. Biol. Chem., February 4, 2005; 280(5): 3963 - 3973. [Abstract] [Full Text] [PDF]