Journal of Cell Science, Vol 112, Issue 4 477-489, Copyright © 1999 by Company of Biologists

JOURNAL ARTICLES

N-Ras induces alterations in Golgi complex architecture and in constitutive protein transport

T Babia, I Ayala, F Valderrama, E Mato, M Bosch, JF Santaren, J Renau-Piqueras, JW Kok, TM Thomson and G Egea
Departament de Biologia Cel.lular, Facultat de Medicina, IDIBAPS, Universitat de Barcelona, C/Casanova, 08036 Barcelona (Spain). egea@medicina.ub.es

Aberrant glycosylation of proteins and lipids is a common feature of many tumor cell types, and is often accompanied by alterations in membrane traffic and an anomalous localization of Golgi-resident proteins and glycans. These observations suggest that the Golgi complex is a key organelle for at least some of the functional changes associated with malignant transformation. To gain insight into this possibility, we have analyzed changes in the structure and function of the Golgi complex induced by the conditional expression of the transforming N-Ras(K61) mutant in the NRK cell line. A remarkable and specific effect associated with this N-Ras-induced transformation was a conspicuous rearrangement of the Golgi complex into a collapsed morphology. Ultrastructural and stereological analyses demonstrated that the Golgi complex was extensively fragmented. The collapse of the Golgi complex was also accompanied by a disruption of the actin cytoskeleton. Functionally, N-Ras-transformed KT8 cells showed an increase in the constitutive protein transport from the trans-Golgi network to the cell surface, and did not induce the appearance of aberrant cell surface glycans. The Golgi complex collapse, the actin disassembly, and the increased constitutive secretion were all partially inhibited by the phospholipase A2 inhibitor 4-bromophenylacyl bromide. The results thus suggest the involvement of the actin cytoskeleton in the shape of the Golgi complex, and intracellular phospholipase A2 in its architecture and secretory function.
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