Multicompartmental distribution of the tuberous sclerosis gene products, hamartin and tuberin
| Autor: | Kathryn A Jones, Atis Muehlenbachs, Raymond S. Yeung, Baldwin C. Mak, Yuji Yamamoto |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Macromolecular Substances Caveolin 1 Biophysics Biology Kidney Biochemistry Caveolins Tuberous Sclerosis Complex 1 Protein Cell Line Tuberous sclerosis Cytosol Tuberous Sclerosis Caveolae Microsomes Testis Tuberous Sclerosis Complex 2 Protein medicine Animals Humans Molecular Biology Cytoskeleton rab5 GTP-Binding Proteins Brain Chemistry Tumor Suppressor Proteins Peripheral membrane protein Lipid microdomain Membrane Proteins Proteins rap1 GTP-Binding Proteins medicine.disease Rats Inbred F344 Cell biology Cell Compartmentation Rats Vesicular transport protein Repressor Proteins Protein Transport medicine.anatomical_structure Liver Cytoplasm Organ Specificity TSC1 TSC2 Spleen Subcellular Fractions |
| Zdroj: | Archives of biochemistry and biophysics. 404(2) |
| ISSN: | 0003-9861 |
| Popis: | Mutations of the TSC1 and TSC2 genes give rise to the clinical disorder of tuberous sclerosis characterized by the development of hamartomas predominantly affecting the central nervous system, kidney, skin, lung, and heart. The function of the gene products, hamartin and tuberin, is not well understood but we have previously suggested a role in vesicular transport. To define the subcellular compartment(s) involved with these two proteins, biochemical characterization of hamartin and tuberin was performed in primary tissues and cell lines. Fractionation of cell lysates identified both proteins in the cytosolic, microsomal, and cytoskeletal compartments. In each of these fractions, hamartin and tuberin formed a stable complex in coimmunoprecipitation analyses. Further, they colocalized extensively in discrete, vesicular structures in the cytoplasm. Within the microsomal compartment, hamartin and tuberin behaved as peripheral membrane proteins that associate with the cytosolic leaflet of membranous domains. Immunoisolation of tuberin-bound vesicles using magnetic beads showed an enrichment of rap1, rab5, and caveolin-1, all of which have been found in specialized lipid microdomains, caveolae. Our data suggest that hamartin and tuberin are multicompartmental proteins that partially reside in caveolin-1-enriched structures and potentially affect their signaling. |
| Databáze: | OpenAIRE |
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