INVESTIGADORES
BOLLO Mariana Ines
congresos y reuniones científicas
Título:
GM2-ganglioside accumulation mediates Endoplasmic Reticulum Ca2+ depletion and PERK signalling activation
Autor/es:
VIRGOLINI, M.J. LOPEZ, PHH AND BOLLO M..
Lugar:
Huerta Grande
Reunión:
Congreso; XXVIII Congreso Anual de Investigación Neurociencia y Reunión satélite/neurobiología del comportamiento: neuroetología y neurobiología de la memoria en el Conosur; 2013
Institución organizadora:
Sociedad Argentina de Neurociencia
Resumen:
<!--
/* Font Definitions */
@font-face
{font-family:Arial;
panose-1:2 11 6 4 2 2 2 2 2 4;
mso-font-charset:0;
mso-generic-font-family:auto;
mso-font-pitch:variable;
mso-font-signature:-536859905 -1073711037 9 0 511 0;}
@font-face
{font-family:"Courier New";
panose-1:2 7 3 9 2 2 5 2 4 4;
mso-font-charset:0;
mso-generic-font-family:auto;
mso-font-pitch:variable;
mso-font-signature:-536859905 -1073711037 9 0 511 0;}
@font-face
{font-family:Times;
panose-1:2 0 5 0 0 0 0 0 0 0;
mso-font-charset:0;
mso-generic-font-family:auto;
mso-font-pitch:variable;
mso-font-signature:3 0 0 0 1 0;}
@font-face
{font-family:Calibri;
panose-1:2 15 5 2 2 2 4 3 2 4;
mso-font-charset:0;
mso-generic-font-family:auto;
mso-font-pitch:variable;
mso-font-signature:-520092929 1073786111 9 0 415 0;}
/* Style Definitions */
p.MsoNormal, li.MsoNormal, div.MsoNormal
{mso-style-unhide:no;
mso-style-qformat:yes;
mso-style-parent:"";
margin-top:0in;
margin-right:0in;
margin-bottom:10.0pt;
margin-left:0in;
line-height:115%;
mso-pagination:widow-orphan;
font-size:11.0pt;
font-family:Calibri;
mso-fareast-font-family:Calibri;
mso-bidi-font-family:"Times New Roman";
mso-ansi-language:ES-AR;}
.MsoChpDefault
{mso-style-type:export-only;
mso-default-props:yes;
font-size:10.0pt;
mso-ansi-font-size:10.0pt;
mso-bidi-font-size:10.0pt;
font-family:Calibri;
mso-ascii-font-family:Calibri;
mso-fareast-font-family:Calibri;
mso-hansi-font-family:Calibri;}
@page WordSection1
{size:8.5in 11.0in;
margin:1.0in 1.25in 1.0in 1.25in;
mso-header-margin:.5in;
mso-footer-margin:.5in;
mso-paper-source:0;}
div.WordSection1
{page:WordSection1;}
-->
The accumulation of misfolded proteins within
the endoplasmic reticulum (ER) triggers a cellular process known as the Unfolded Protein Response (UPR), in which the cell attempts to restore ER
homeostasis. If ER damage is persistent or excessive, an apoptotic
response is initiated. It is well accepted that ER
Ca2+ depletion induces ER stress. PERK is an early ER stress sensor that attenuates protein
synthesis. We demonstrated in Xenopus oocytes that Calcineurin (CN) associates with PERK, enhancing inhibition
of protein translation and cell viability. But, PERK signaling,
including pro-apoptotic transcription factor CHOP, persists activated
under prolonged stress. Chronic UPR is proposed to contribute to the pathology
of many neurodegenerative diseases.
GM2-gangliosidosis are characterized by a progressive neurodegeneration. However,
the mechanisms that determine how GM2 accumulation triggers neuronal cell death
remain unknown. Here, we report, by thin layer
chromatography and immunocytochemistry
approaches, that N2a neurons loaded with exogenous ganglioside, accumulates GM2
at ER membranes. The abnormal GM2 build-up induces PERK activation, and
provokes up-regulation of either CN or CHOP, at different time points. This
stress also decreases the ER calcium content in Fura2-loaded cells. Moreover,
calcium depletion, as well as, Chop level increase, induced by GM2
accumulation, was enhanced by MBCD, a pharmacological agent that increase
ganglioside delivery to the ER.