A family of proteins with gamma-adaptin and VHS domains that facilitate trafficking between the trans-Golgi network and the vacuole/lysosome.

We have cloned and characterized members of a novel family of proteins, the GGAs. These proteins contain an NH(2)-terminal VHS domain, one or two coiled-coil domains, and a COOH-terminal domain homologous to the COOH-terminal "ear" domain of gamma-adaptin. However, unlike gamma-adaptin, the GGAs are not associated with clathrin-coated vesicles or with any of the components of the AP-1 complex. GGA1 and GGA2 are also not associated with each other, although they colocalize on perinuclear membranes. Immunogold EM shows that these membranes correspond to trans elements of the Golgi stack and the TGN. GST pulldown experiments indicate that the GGA COOH-terminal domains bind to a subset of the proteins that bind to the gamma-adaptin COOH-terminal domain. In yeast there are two GGA genes. Deleting both of these genes results in missorting of the vacuolar enzyme carboxypeptidase Y, and the cells also have a defective vacuolar morphology phenotype. These results indicate that the function of the GGAs is to facilitate the trafficking of proteins between the TGN and the vacuole, or its mammalian equivalent, the lysosome.

Gamma-synergin: an EH domain-containing protein that interacts with gamma-adaptin.

The AP-1 adaptor complex is associated with the TGN, where it links selected membrane proteins to the clathrin lattice, enabling these proteins to be concentrated in clathrin-coated vesicles. To identify other proteins that participate in the clathrin-coated vesicle cycle at the TGN, we have carried out a yeast two- hybrid library screen using the gamma-adaptin subunit of the AP-1 complex as bait. Two novel, ubiquitously expressed proteins were found: p34, which interacts with both gamma-adaptin and alpha-adaptin, and gamma-synergin, an alternatively spliced protein with an apparent molecular mass of approximately 110-190 kD, which only interacts with gamma-adaptin. gamma-Synergin is associated with AP-1 both in the cytosol and on TGN membranes, and it is strongly enriched in clathrin-coated vesicles. It binds directly to the ear domain of gamma-adaptin and it contains an Eps15 homology (EH) domain, although the EH domain is not part of the gamma-adaptin binding site. In cells expressing alpha-adaptin with the gamma-adaptin ear, a construct that goes mainly to the plasma membrane, much of the gamma-synergin is also rerouted to the plasma membrane, indicating that it follows AP-1 onto membranes rather than leading it there. The presence of an EH domain suggests that gamma-synergin links the AP-1 complex to another protein or proteins.

Surgical management of primary retroperitoneal sarcoma.

BACKGROUND: Retroperitoneal sarcoma is a rare and challenging group of diseases for surgeons, characterized by extensive growth and high recurrent rate. We analyzed data from our patients to identify the factors of survival. METHODS: From 1971 to 1993, medical records of 40 patients with primary retroperitoneal sarcoma were reviewed. Clinical factors including age, sex, tumor size, histopathology, type of operation, disease-free interval, and number of operation were collected to correlate with patient's survival. RESULTS: Most patients presented with huge abdominal mass. There were 22 liposarcomas, 8 leiomyosarcomas, 5 malignant fibrous histiocytomas, 2 fibrosarcomas, 2 malignant mesenchymomas and one rhabdomyosarcoma. Twenty-eight patients received complete resection and 12 had incomplete resection. The group with complete resection showed a better survival than incomplete resection group (p = 0.0001). Nineteen patients with complete resection had tumor recurrence. The recurrent rate was 68%. Patients having been disease-free for more than 12 months showed to have better survival than those less than 12 months (p = 0.005). Aggressive surgical resection was done in case of tumor recurrence. Patients who received more than 2 (> or = 3) operations also showed a better survival than those with less than 2 operations (p = 0.0247). CONCLUSIONS: Complete surgical resection and aggressive repeated surgical intervention are the most effective treatment modality for better survival in patients with retroperitoneal sarcoma.

Alternative donor site for alveolar bone grafting in adults with cleft lip and palate.

Grafting of the alveolar ridge with autogenous bone is an integral stage of contemporary management of complete cleft lip and palate cases. Alveolar bone grafting restores continuity of the dental arch, closes oronasal fistulae, supports the alar base, and facilitates spontaneous eruption of permanent teeth adjacent to the cleft. However, timing of the graft and the selection of materials have been topics of much debate in the literature. This article discusses an alternative donor site in cases where rehabilitation has passed the recommended time. Harvesting bone from the third molar regions allows not only the removal of impacted third molars during the same surgical procedure, but also eliminates the morbidity associated with additional surgical sites such as the ilium or mandibular symphysis. This report should not be interpreted as a recommendation for the use of this alternative site in cases where grafting is carried out within the optimal time period, which is usually in the mixed dentition stage. However, when grafting is necessary in young adults suffering from complete cleft lip and palate, the third molar region may provide another acceptable donor site.