Indra Chandrasekar, PhD, Lab
Primary Research Focus
Chandrasekar lab’s research interest is to understand the role of cytoskeletal proteins in cell and organ function. The Chandrasekar research laboratory is trying to answer some fundamental questions in cellular trafficking pathways and extend those findings to organ function and human diseases. The primary focus of the cell-organ function relationships is aimed at the disorders of kidney and the brain. Our research will (hopefully) uncover some novel cellular and molecular mechanisms involved in chronic kidney diseases and neurodegenerative disorders that will facilitate development of future targeted therapies.
Behind the Research
Cells have compartmentalized structures and rely on regulated membrane trafficking to move cargo between organelles/compartments. Many essential cellular processes such as nutrient uptake, receptor mediated signaling and synaptic vesicle recycling depend on membrane trafficking and endocytosis. Our lab is interested in the role of actin cytoskeleton and actin associated proteins in membrane trafficking and endocytic mechanisms in cells. Recently, we demonstrated that nonmuscle myosin II (MII), an actin associated motor protein is critical for both compensatory and constitutive receptor mediated endocytosis in neurons and fibroblasts. Our work provided the first cellular and genetic evidence for the importance of actin-MII interactions during early stages of clathrin coated vesicle formation. Our current model is that MII regulates endocytosis by forming a contractile network with actin, around the site of membrane remodeling and acting like a purse string to regulate the curvature and scission processes, thereby aiding in vesicle budding (Fig.1). Identifying MII as a critical player in endocytosis has raised the following questions:
Our work on primary neurons indicates that MII-driven tension/actin dynamics regulate the major pathway of synaptic vesicle retrieval (clathrin mediated compensatory endocytosis) and is critical for synaptic transmission. This suggests a unique and essential role for actin-MII mediated tension in cell types that require rapid and continuous membrane remodeling to perform essential organ function. We are interested in understanding the cell type specific requirements for dynamic cytoskeletal changes in cells that populate organs like kidney and brain.