Advances in Brief Hiimartin, the Product of the Tuberous Sclerosis l (TSC1} Gene, Interacts with Tuberin and Appears to Be Localized to Cytoplasmic Vesicles1

Tuberous sclerosis is an inherited syndrome associated with mutations in two tumor suppressor genes: TSCI and TSC2. Tuberin, the product of TSC2, appears to be localized to the Golgi apparatus and may have a function in vesicular transport. The function of hamartin, the product of TSCI, is not known. In this report, we demonstrate an interaction between hamartin and tuberin, which is detectable at endogenous protein levels. Hamartin is present in a cell line derived from the Eker rat that lacks functional tuberin, indicating that the stability of hamartin is not depend ent on its interaction with tuberin. Hamartin is localized to the membrane/ particulale (PI(H)) fraction of cultured cells. The I"I(10 localization is unchanged in the Eker cells. Finally, we show that at endogenous expres sion levels, hamartin has a punctate pattern of immunofluorescence in the cytoplasm. Taken together, the presence of hamartin in the membrane/ participate fraction and its pattern of cytoplasmic staining suggest that it is localized to cytoplasmic vesicles. If altered vesicular trafficking leads to tumorigenesis in tuberous sclerosis, TSCI and TSC2 may have a novel mechanism of tumor suppression