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Mechanobiology of Disease
Poster Abstracts
68
73-POS
Board 73
Role and Regulation of Caveolae in Three-dimensional Environment
Trupti Thite
, Natasha Buwa, Nagaraj Balasubramanian.
Indian Institute of Science Education and Research (IISER), Pune, Maharashtra, India.
Caveolae are 60-80 nm omega shaped structures on the plasma membrane which comprise
Caveolin-1 (Cav1) as a major structural protein and are rich in cholesterol and sphingolipids.
Caveolae play an important role in cellular signaling, endocytosis and mechanosensing. Apart
from these functions, caveolae have been recently emerged as plasma membrane organizers and
protectors. Their presence or absence changes the membrane composition, membrane order and
membrane tension, further regulating signal transduction in cells.These properties of plasma
membrane are either known or expected to be different in cells which are cultured in a three-
dimensional (3D) microenvironment as compared to conventional rigid two-dimensional (2D)
tissue culture plate. The role and regulation of caveolae, is not known in cells grown in a 3D
microenvironment and that is the focus of this study. Our studies show that, in Mouse Embryonic
Fibroblasts (MEFs) embedded in a collagen gel, the loss of Cav1, and hence caveolae results in
increased mobility of two membrane markers, K-Ras-CAAX-GFP and GPI-GFP. Reconstitution
of Cav1-KO MEFs with WT-Cav1 reverses the increased mobility of both the markers. Another
aspect of this study shows that Cav1 (but not its phosphorylation) negatively regulates
endocytosis of certain cargos in MEFs embedded in 3D. This differential regulation of
endocytosis is dependent on collagen matrix concentration. The mechanism of this differential
regulation of endocytosis is currently being explored. Cav1 is a known tumor suppressor and the
role it has in mediating differential trafficking and endocytosis in cancer cells in 3D matrices is
also something we are actively exploring.