Three GGAs (GGA1-3) were found in humans, among which GGA3 has short and long forms of spliced variants (GGA3-S and GGA3-L). The present study analyzed expression patterns of both GGA3 variants in human tissues and cell lines. Western blot analysis revealed that the brain contained both GGA3-S and -L, while other tissues and cell lines examined predominantly expressed GGA3-S. By double immunofluorescence microscopy, GGA1 and GGA3 were localized with slightly different patterns in both the trans-Golgi network (TGN) and peripheral region. When the dominant-negative mutant, VHS-GAT domain, of GGA1 or GGA3-L was overexpressed, TGN-associated GGA1 was redistributed into the cytoplasm. However, the GGA3 distribution was not affected by the expression of either VHS-GAT domain. These results indicate that GGA3-S which would not be directly involved in the cargo protein recognition is predominantly expressed in human tissues except the brain and in cell lines. (C) 2003 Elsevier Science (USA). All rights reserved.