Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles

• Published in: Cancer research (Chicago, Ill.) Vol. 58; no. 21; pp. 4766 - 4770
• Main Authors: PLANK, T. L, YEUNG, R. S, HENSKE, E. P
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.11.1998
• Subjects: Animals; Biological and medical sciences; Cell Line; Cell Membrane - chemistry; Cell structures and functions; Cytoplasm - chemistry; Fundamental and applied biological sciences. Psychology; Golgi apparatus; Humans; Microscopy, Confocal; Molecular and cellular biology; Molecular Weight; Precipitin Tests; Proteins - analysis; Proteins - metabolism; Rabbits; Rats; Repressor Proteins - physiology; Tumor Suppressor Proteins; Human; Nervous system diseases; Rat; Gene product; Rodentia; Biomembrane; Gene expression; In vitro; Biological activity; Genetic disease; Vertebrata; Mammalia; Tuberin; Animal; Established cell line; Tumor; Bourneville syndrome; Tumor cell; Tumor suppressor gene; Cytoplasmic vesicle
• ISSN: 0008-5472; 1538-7445

Tuberous sclerosis is an inherited syndrome associated with mutations in two tumor suppressor genes: TSC1 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 TSC1, 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 dependent on its interaction with tuberin. Hamartin is localized to the membrane/particulate (P100) fraction of cultured cells. The P100 localization is unchanged in the Eker cells. Finally, we show that at endogenous expression levels, hamartin has a punctate pattern of immunofluorescence in the cytoplasm. Taken together, the presence of hamartin in the membrane/particulate 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, TSC1 and TSC2 may have a novel mechanism of tumor suppression.