Regulation of Selective Endocytic Transport

Colorado State University, Fort Collins CO

Investigators

Abstract

Intellectual Merit Cells must take up nutrients, communicate with the external environment, and quickly adapt to changes in environmental conditions. To carry out these tasks, the composition of the cell surface (the plasma membrane) is continually adjusted. Through the process of exocytosis, the cell delivers newly synthesized molecules to the plasma membrane or the extracellular space. By the opposite process called endocytosis cells internalize surface components. For example, cells utilize endocytosis to take up nutrients, such as iron, vitamins, and lipids bound by receptors embedded in the plasma membrane. Once inside the cell, the nutrients are released from the receptors and used in various biosynthetic processes. During endocytosis, a portion of the plasma membrane is pulled into the inside of the cell forming a small, spherical structure known as an endocytic vesicle. Various cellular components are in charge of: (1) selecting which receptors and other membrane proteins will be internalized; (2) bending the membrane to generate the incipient endocytic vesicle; and (3) providing the force to pull the vesicle into the cell. Fundamental cellular components known as adaptor proteins, clathrin, and the actin cytoskeleton mediate the three steps of endocytic vesicle formation. This laboratory is studying the molecular mechanisms by which adaptor proteins, clathrin and the actin cytoskeleton carry out the endocytic process. Specifically, this project focuses on how the three steps are mechanistically and temporally coordinated. These cellular components and the endocytic process they mediate are conserved in all eukaryotic cells and are essential for life. The research is carried out using yeast cells, a superb model system amenable to a wide range of experimental strategies. Broader Impacts The project will have broad impacts in several ways: (i) This project will contribute to increase diversity in science and education. This project will support: an under-represented minority PhD student, an outstanding female Research Assistant Professor from an under-represented group, and undergraduate students from a largely minority serving institution who will participate in summer research experiences (REU program) in the laboratory. The project will also support a minority Assistant Professor actively involved in the Colorado Alliance for Graduate Education and the Professoriate, a program seeking to increase the number of minority students historically under-represented in obtaining graduate degrees in Science, Technology, Engineering, and Mathematics (STEM disciplines). (ii) The graduate and undergraduate students who conduct the studies will be trained in widely used techniques, critical thinking, and presentation skills through writing reports and manuscripts, giving departmental seminars, and attending scientific conferences. (iii) Both undergraduate and graduate students in this project will be involved in taking endocytosis studies and fluorescence microscopy into middle school classrooms. This outreach activity is initiated in a bilingual English/Spanish middle school program attended by numerous under-represented minority children. The students will observe different parts of the cell with a fluorescence microscope and perform experiments designed to teach them basic cell biology concepts and spark their interest in science. (iv) Results from this project will be published in scientific journals, and presented at both specialized conferences and national cell biology meetings, thus impacting the broader scientific community.