SEP 23, 2020 12:00 PM PDT

Keynote Presentation: Sorting out the mechanisms of endocytic recycling

Presented at: Cell Biology 2020
C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Professor and Vice Chair for Administration, Dept. of Biochemistry and Molecular Biology, Director, UNMC Advanced Microscopy Core Facility, Research Institute-Program Coordinator
    Biography

      Steve Caplan received his PhD from the Lautenberg Center for Tumor and General Immunology at the Hebrew University Hadassah Medical Center, Jerusalem, Israel,  in 1998. He trained as a postdoctoral fellow between 1998 and 2003 at the National Institutes of Health, before accepting a faculty position in the Department of Biochemistry and Molecular Biology at the University of Nebraska Medical Center (UNMC) in Omaha, Nebraska in 2003. Dr. Caplan is currently a Professor and Vice Chair for Administration, and serves as the Director of the UNMC Advanced Microscopy Core Facility, as well as the Research Institute-Program Coordinator for the Nebraska INBRE Program, an NIH-funded program designed to improve the research infrastructure for the state of Nebraska and to encourage and promote undergraduate science research. Dr. Caplan has received multiple awards, including Outstanding Faculty Mentor of Graduate Students, UNMC Distinguished Scientist and the Thomas Maciag award for mentorship and research. Dr. Caplan is the author of about 100 published manuscripts, as well as 4 novels of fiction that deal with the lives of scientists, and has written a series of articles for newspapers such as The Guardian in the UK.


    Abstract

    Extracellular ligands bind to receptors on the cell surface leading to receptor internalization. Once internalized into small vesicles, the vesicles fuse with an organelle known as the sorting endosome (SE). The SE is a sorting station that directs receptors to different pathways, in part by sorting nexin (SNX) proteins. Notably, SNX17 interacts with a multitude of receptors in a sequence-specific manner to regulate their recycling. However, the mechanisms by which SNX17-labeled vesicles that contain sorted receptors bud and undergo vesicular fission from the SE remain elusive. Recent studies suggest that a dynamin-homolog, EHD1, catalyzes fission and releases endosome-derived vesicles for recycling to the plasma membrane. However, the mechanism by which EHD1 is coupled to various receptors and regulates their recycling remains unknown. Herein, we seek to characterize the mechanism by which EHD1 couples with SNX17 to regulate the recycling of SNX17-interacting receptors. Our central hypothesis is that SNX17 couples receptors to the EHD1 fission machinery. Co-immunoprecipitations and in vitro assays provide evidence that EHD1 and SNX17 directly interact. We also found that inducing internalization of a SNX17 cargo receptor, Low Density Lipoprotein Receptor Related Protein 1  (LRP1) led to recruitment of cytoplasmic EHD1 to endosomal membranes.  In addition, 3D surface rendering and quantification of overlap volumes demonstrate that SNX17 and EHD1 partially co-localize on endosomes, and this overlap was further increased upon LRP1 internalization. Moreover, SNX17-containing endosomes were larger in EHD1-depleted cells compared to wild-type cells, suggesting that EHD1 depletion impairs SNX17-endosomal fission. This study helps clarify our current understanding of endocytic trafficking, by providing significant new insight into the process of endosomal fission and connecting the sorting and fission machineries.

    Learning Objectives:

    1. Define the process by which endocytic trafficking occurs

    2. Explain the mechanism by which endosomal fission is mediated


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