Regulated membrane and protein transport is a central component of a multitude of biological processes and is critically important in human heath. For example, transport defects are implicated in hypercholesterolemia, Huntington's disease, and myeloid leukemia. Thus, elaborating molecular mechanisms of membrane trafficking are profoundly important to both basic and applied research. Our interests are in exploiting advantageous features of C. elegans and mammalian cells to investigate one of the least understood steps in endocytic traffic-the return of internalized molecules to the cell surface via recycling endosomes. Surprisingly little is known of the molecules that mediate and regulate this step of recycling. Initial studies indicate this process is highly conserved in metazoans, and may be distinct from related processes in microbes like yeast. Using a genetic approach in C. elegans, we have identified novel proteins that are critical for the recycling process in vivo. One of these, RME-1, is a peripheral membrane protein of the recycling endosome that regulates export from the recycling endosome in a process thought to utilize membrane tubules. RME-1 appears highly conserved between nematodes and mammals in both structure and basic function and is one of the first proteins clearly implicated in this specific recycling step. Mutations in a second protein, GUM-l, cause the same biological defects as mutations in RME-I. Furthermore, GUM-1 is required for the localization of RME-1 to endosomes. The molecular identity of the GUM-1 protein and the mechanism by which it regulates RME-1 localization are currently unknown. We plan to decipher the biology of endocytic recycling by conducting an in-depth multi-pronged analysis of RME-1 and GUM-1 and by applying novel approaches toward the identification of additional proteins that act with RME-1 and GUM-1 in the process of recycling.
Our specific aims are: l) To test key working hypotheses that RME-1 is regulated by nucleotide binding and membrane association, and that RME-1 participates in membrane tubule formation. 2) To characterize GUM-l, a novel regulator of endocytic recycling in C. elegans and mammals. 3) To identify additional mediators and regulators of endocytic recycling in C. elegans. By combining the power of C. elegans genetics and mamalian cell biology this work will significantly advance our understanding of .the mechanisms determining a key metazoan membrane transport process.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-CDF-4 (02))
Program Officer
Shapiro, Bert I
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Rutgers University
Schools of Arts and Sciences
New Brunswick
United States
Zip Code
Zhang, Junbing; Liu, Jinchao; Norris, Anne et al. (2018) A novel requirement for ubiquitin-conjugating enzyme UBC-13 in retrograde recycling of MIG-14/Wntless and Wnt signaling. Mol Biol Cell 29:2098-2112
Norris, Anne; Tammineni, Prasad; Wang, Simon et al. (2017) SNX-1 and RME-8 oppose the assembly of HGRS-1/ESCRT-0 degradative microdomains on endosomes. Proc Natl Acad Sci U S A 114:E307-E316
Palmisano, N J; Rosario, N; Wysocki, M et al. (2017) The recycling endosome protein RAB-10 promotes autophagic flux and localization of the transmembrane protein ATG-9. Autophagy 13:1742-1753
Gleason, Adenrele M; Nguyen, Ken C Q; Hall, David H et al. (2016) Syndapin/SDPN-1 is required for endocytic recycling and endosomal actin association in the C. elegans intestine. Mol Biol Cell :
Balklava, Zita; Rathnakumar, Navin D; Vashist, Shilpa et al. (2016) Linking Gene Expression in the Intestine to Production of Gametes Through the Phosphate Transporter PITR-1 in Caenorhabditis elegans. Genetics 204:153-62
Wang, Peixiang; Liu, Hang; Wang, Yu et al. (2016) RAB-10 Promotes EHBP-1 Bridging of Filamentous Actin and Tubular Recycling Endosomes. PLoS Genet 12:e1006093
Liu, Ou; Grant, Barth D (2015) Basolateral Endocytic Recycling Requires RAB-10 and AMPH-1 Mediated Recruitment of RAB-5 GAP TBC-2 to Endosomes. PLoS Genet 11:e1005514
Bai, Zhiyong; Grant, Barth D (2015) A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic recycling. Proc Natl Acad Sci U S A 112:E1443-52
Sato, Ken; Norris, Anne; Sato, Miyuki et al. (2014) C. elegans as a model for membrane traffic. WormBook :1-47
Gleason, Ryan J; Akintobi, Adenrele M; Grant, Barth D et al. (2014) BMP signaling requires retromer-dependent recycling of the type I receptor. Proc Natl Acad Sci U S A 111:2578-83

Showing the most recent 10 out of 56 publications