Tuberous sclerosis hamartin and tuberin protein complex in renal epithelial cells.

• Grant number: 09/04053-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2009
• End date: September 30, 2011
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Luiz Fernando Onuchic
• Grantee: Crysthiane Saveriano Rubião Silva
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 98/14254-2 - The Human Genome Research Center, AP.CEPID

Abstract

Tuberous sclerosis complex (TSC) is a hamartomatosis due to mutations in either tumor suppressor gene, TSC1 or TSC2, which codes for hamartin and tuberin, respectively. These proteins form a macromolecular, cytosolic complex that regulates cell proliferation, differentiation, growth and migration, aspects commonly deficient in TSC hamartoma cells. Although TSC hamartomas may affect any organ, highest morbidity is associated with brain, kidney or lung lesions. Renal epithelial lesions may be cystic, bilateral, numerous, and due to polarization, adhesion, and migration deficits. We have established in our laboratory tridimmensional cultures of kidney collecting duct cells which present high endogenous levels of hamartin and tuberin expression. The mouse immortalized cell line, IMCD, cultivated in collagen type I led to the formation of tubules of simple epithelia. Culturing conditions have been reported to yield cysts instead of tubules. This proposal aims to analyze by immunofluorescence the 3D structural patterns achieved by culturing IMCD in Matrigel as compared to collagen type I, as well as after the addition of trophic factors such as hepatocyte-derived growth factor, HGF, a known tubulogenic factor. We will compare (i) hamartin and tuberin expression in IMCD cells under the various conditions; and (ii) the interaction between them and with other known partners such as the actin filament regulator, ezrin, and the target of rapamycin regulator and tuberin interactor Rheb, a small GTPase.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVA, Crysthiane Saveriano Rubião. Apoptosis, late synchronous cell proliferation and expression profile of TSC and PKD proteins during in vitro tubulogenesis. 2013. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.