IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
ER calcium regulates the intracellular localization of calreticulin
Autor/es:
MÁXIMO LÓPEZ MEDUS; CARLOS LABRIOLA; ANA VILLAMIL GIRALDO; RODRIGO PAGANO; ARMANDO J. PARODI; JULIO CARAMELO
Lugar:
Viña del Mar-Chile
Reunión:
Simposio; 8th International Calreticulin Workshop; 2009
Institución organizadora:
International Calreticulin Workshop
Resumen:
<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-bidi-font-family:"Times New Roman"; mso-bidi-language:AR-SA;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> ER calcium regulates the intracellular localization of calreticulin   Máximo López Medus1, Carlos Labriola2, Ana Villamil Giraldo3, Rodrigo S. Pagano4, Armando J. Parodi5 and Julio J. Caramelo6   1-6Fundación Instituto Leloir, 1-6Instituto de Investigaciones Bioquímicas de Buenos Aires (CONICET) and 1Biologycal Chemistry Department - School of Sciences - University of Buenos Aires   Although CRT main intracellular localization is the ER, several reports have also found it in the plasma membrane, secretory granules, cytosol and nucleus. The main functions of CRT in the ER are those of lectin/chaperone and calcium buffering, while its role in other locations remains obscure. The calcium buffering activity of CRT is located at the C-terminal domain, and an additional high affinity calcium binding site resides in the N-terminal domain. The calcium ion at this last site fulfils a structural role and is not involved in sugar binding. We have recently shown that the lectin activity of CRT is independent from its calcium buffering activity, bringing about the reasons of maintaining two very important functions in the same polypeptide. Here we show that ER calcium levels regulate the localization of CRT. Inhibition of the ER calcium pump SERCA or agonist-induced generation of inositol triphosphate dramatically increases the level of cytosolic CRT. This change is also observed in cells pretreated with cycloheximide, pointing to a retrotranslocation process rather than an inefficient initial translocation into the ER during CRT synthesis. This behavior is strictly dependent on CRT C-terminal domain, since a truncated form of CRT lacking this domain remained entirely in the ER, while unrelated proteins fused to this domain display an intracellular localization behavior similar to that of CRT. We propose a molecular mechanism and some possible functions for this process.