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Báo cáo khoa học: Membrane distribution of epidermal growth factor receptors in cells expressing different gangliosides

Gangliosideshavebeen found toreside inglycosphingolipid-enriched microdomains (GEM) of the plasma membrane and to be involved in the regulation of epidermal growth factor receptor (EGFr or ErbB1) activity.To gain further insight into the mechanisms involved in EGFr modulation by gangliosides, we investigated the distribution of EGFr family members in the plasma membrane of CHO-K1 cells, which were genetically modified to express different gan-glioside molecules or depleted of glycolipids. | Eur. J. Biochem. 271 2428-2437 2004 FEBS 2004 doi 10.1111 j.1432-1033.2004.04165.x Membrane distribution of epidermal growth factor receptors in cells expressing different gangliosides Adolfo R. Zurita1 Pilar M. Crespo1 Nicolas P. Koritschoner2 and Jose L. Daniotti1 1Centro de Investigaciones en Quimica Biologica de Córdoba CIQUIBIC UNC-CONICET Departamento de Quimica Biológica Facultad de Ciencias Quimicas Universidad Nacional de Cordoba Argentina 2Departamento de Bioquimica Clinica Facultad de Ciencias Quimicas Universidad Nacional de Cordoba Argentina Gangliosides have been found to reside in glycosphingolipid-enriched microdomains GEM of the plasma membrane and to be involved in the regulation of epidermal growth factor receptor EGFr or ErbB1 activity. To gain further insight into the mechanisms involved in EGFr modulation by gangliosides we investigated the distribution of EGFr family members in the plasma membrane of CHO-K1 cells which were genetically modified to express different ganglioside molecules or depleted of glycolipids. Our data demonstrate that at least four different sets of endogenously expressed gangliosides including GD3 did not have a significant effect on EGFr distribution in the plasma membrane. In addition using confocal mirroscopy analysis we clearly demonstrated that the EGFr co-localizes only to a minor extent with GD3. We ako expOoeed the endogenous expression in wild-type CHO-K1 cells of the orphan receptor ErbB2 which is the preferred heteroassociation partner of all other ErbB proteins and the effect of GD3 expression on its membrane distribution. Our resu111s showed that CHO-K1 cells endogenously express ErbB2 and that expression of the GD3 affected to some extent the membrane distribution of endogenous ErbB2. Finalỉy our findings support the notion that most EGFr are excluded from GEM while an important fraction of ErbB2 is found to be associated with these microdomains in membranes from CHO-K1 cells. Keywords gangliosides EGFr .