Townsend SR et al. (1994) Worm Breeder's Gazette "C. elegans Molecular Genetics and Long PCR."

Finelli AL, Savage C, Xie T, Padgett RW, Townsend SR

[Worm Breeder's Gazette, 1994]

C. elegans Molecular Genetics and Long PCR Scott R. Townsend, Cathy Savage, Alyce L. Finelli, Ting Xie, and Richard W. Padgett, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08855

Gleason, Ryan et al. (2011) International Worm Meeting "Intracellular trafficking of the type I and type II TGFb receptors, SMA-6 and DAF-4, in C. elegans."

Grant, Barth, Akintobi, Adenrele, Padgett, Richard, Gleason, Ryan

[International Worm Meeting, 2011]

Receptor-mediated endocytosis regulates the internalization, degradation, and recycling of a diverse group of membrane bound, cell-signaling receptors. This regulation of cell signaling receptors modulates receptor availability, duration of signaling, and signaling strength. We have been developing C. elegans as a model to study the trafficking of TGFb receptors SMA-6 and DAF-4. Interestingly, using endocytic mutations that block recycling and transport to the trans-Golgi network (TGN), we find that trafficking of the type I and type II receptors are handled differently in the animal. Mutations in vps-35, a component of the retromer, block C. elegans TGFb signaling, indicating that retromer recycling of one or both receptors is necessary for full signaling strength. This work was prompted by the identification of sma-10, which was discovered through a genetic screen in the Padgett Lab, and which we show also affects the trafficking of the type I and type II receptors, sma-6 and daf-4. Experiments were done to distinguish between a role in receptor secretion or in internalization of receptors. Using double mutants for the AP-2 complex (required for entry into the cell) and sma-10, we show that sma-10 does not act in secretion of the receptors but acts after receptor internalization. In sma-10 mutants, both receptors accumulate in the cytoplasm, indicating that recycling and/or degradation are altered. Further data will be presented to show how TGFb traffics in C. elegans and what role sma-10 plays in this process.

Gleason, Ryan et al. (2009) International Worm Meeting "Genetic mapping and characterization of a C. elegans Sma mutant."

Byrne, Rich, Padgett, Richard, Gleason, Ryan

[International Worm Meeting, 2009]

The transforming growth factor-b (TGFb) superfamily controls various processes of development and homeostasis of most tissues in metazoan organisms by exploiting the multifunctional TGFb signal transduction pathway. The TGFb superfamily consists of 42 structurally related members including members of the BMP family, TGFb family, activin family, glial derived neurotrophic factor (GDNF) and Mullerian Inhibitory Factor (MIF). The members of this superfamily act most commonly as local mediators to regulate a wide range of biological processes in all organisms. They have been functionally identified as essential regulators of developmental processes including; pattern formation, proliferation, cell division (positive and negative regulators), differentiation, extracellular matrix production, cell migration, cell death, tissue repair, and immune regulation. Aberrant expression of members of the TGFb superfamily has been detected in many diseases and cancer. The TGFb signaling pathways are conserved, and genetic screens in both C. elegans and D. melanogaster have been essential in delineating the transduction pathway. To identify novel members of this signal transduction pathway including receptors, intracellular components, extracellular regulators, and transcription factors we have characterized Sma mutants identified in genetic screens within the lab. wk94, a new allele identified as a novel Sma/Mab mutant has been mapped to chromosome I. wk94, regulates a gene reporter wkEx52 (spp-9::GFP), a reporter for Dbl-1 TGFb signaling, further characterizing its role in TGFb signaling. Efforts are underway to map and clone wk94. Current status will be presented at the meeting.

Vora, Mehul et al. (2015) International Worm Meeting "LRIGs: Novel Regulators of TGF-beta / BMP Signaling."

Padgett, Richard, Kane, Nanci, Gleason, Ryan, Vora, Mehul

[International Worm Meeting, 2015]

Transforming Growth Factor - beta (TGFbeta) / Bone Morphogenetic Protein (BMP) signaling is a conserved signaling pathway that governs fundamental developmental processes across metazoans. In the nematode Caenorhabditis elegans, the pathway controls body size and male tail morphology, but also has functions in innate immunity and aging. In a screen to identify regulators of pathway signaling, we identified the gene sma-10 that appears to interfere with the trafficking of the TGFbeta receptors, after internalization, leading to a decreased signaling output. The Leucine-Rich Immunoglobulin-containing (LRIG1-3) genes are the mammalian orthologs of sma-10. A central question is if sma-10 trafficking effects are conserved in vertebrates. To address these questions, we are utilizing fly and mammalian tissue culture models. We show that overexpression of LRIGs in HeLa cells leads to decreased abundance of co-transfected TGFbeta and BMP receptors. Experiments are underway, using RNAi, to assess the effect of knockdowns of LRIGs on receptor trafficking.

Martinelli SD et al. (1995) International C. elegans Meeting "ACEDB"

Durbin RM, Martinelli SD

[International C. elegans Meeting, 1995]

We hope to provide a demonstration of the current state of the ACeDB worm database on Unix workstations, and if possible Apple Macintosh, throughout the poster sessions. This will be based on the new version 4 release of the acedb software (Jean Thierry-Mieg, Richard Durbin and numerous others), which contains many new features for greater efficiency, more flexible printing, and display of new features.

(2024) Development "The people behind the papers - Thomas Mullan and Richard Poole."

[Development, 2024]

Asymmetric cell divisions can produce daughter cells of different sizes, but it is unclear whether unequal cell cleavage is important for cell fate decisions. A new paper in Development explores the role of unequal cleavages in Caenorhabditis elegans embryos. To learn more about the story behind the paper, we caught up with first author Thomas Mullan and corresponding author Richard Poole, Associate Professor of Developmental Biology at University College London, UK.

Liao, Kelvin et al. (2017) International Worm Meeting "C. elegans SMA-10 regulates BMP Receptor Trafficking."

Liao, Kelvin, Padgett, Richard, Vora, Mehul, Gleason, Ryan, Kane, Nanci, Li, Ying

[International Worm Meeting, 2017]

Signal transduction of the conserved BMP signaling pathway functions through two distinct serine/threonine transmembrane receptors, the type I and type II receptors. Endocytosis orchestrates the assembly of signaling complexes by coordinating the entry of receptors with their downstream signaling mediators. Recently, we showed that the C. elegans type I bone morphogenetic protein (BMP) receptor SMA-6, part of the transforming growth factor- beta (TGF beta ) superfamily, is recycled through the retromer complex unlike the type II receptor, DAF-4. From genetic screens in C. elegans aimed at identifying new modifiers of BMP signaling, we reported on SMA-10, a conserved LRIG (leucine-rich and immunoglobulin-like domains) transmembrane protein. It is a positive regulator of BMP signaling that binds to the SMA-6 receptor. Here we show that the loss of sma-10 leads to aberrant endocytic trafficking of SMA-6, resulting in its accumulation in distinct intracellular endosomes including the early endosome, MVB, and the late endosome with a reduction in signaling strength. Our studies show that trafficking defects caused by the loss of sma-10 are not universal, but affect only a limited set of receptors. Likewise, in Drosophila, we find that the fly homolog of sma-10, lambik (lbk), reduces signaling strength of the BMP pathway, consistent with its function in C. elegans and suggesting evolutionary conservation of function. Loss of sma-10 results in reduced ubiquitination of the type I receptor SMA-6, suggesting a possible mechanism for its regulation of BMP signaling.

Herman RK et al. (1997) Worm Breeder's Gazette "STATUS OF THE CAENORHABDITIS GENETICS CENTER (CGC)"

Herman RK, Stiernagle TL

[Worm Breeder's Gazette, 1997]

May 31, 1997 will mark the end of our current five-year contract with the NIH National Center for Research Resources, which supports the activities of the CGC. The activities in St. Paul have involved primarily the acquisition, maintenance and distribution of stocks and information about stocks, acquisition and maintenance of the C. elegans bibliography, and publication and distribution of The Worm Breeder's Gazette (WBG) and WBG Subscriber Directory. Genetic nomenclature and the genetic map have been managed for the period 1992-1997 by Jonathan Hodgkin (CGC Map Curator) on a subcontract. Currently, the subcontract provides half of Sylvia Martinelli's salary, plus travel and minor expenses. Additional support from within the MRC Laboratory of Molecular Biology and the Sanger Centre has been used to fund other essential resources such as computer equipment, as well as Jonathan's and Richard Durbin's time. Richard has been involved in mapkeeping through his work on ACeDB. We are pleased that Jonathan, Richard and Sylvia agreed to continue their work for another five years. We have submitted an application for a new five year contract that would include a subcontract for nomenclature and mapkeeping on essentially the same terms as before. A description of the nomenclature and mapkeeping activities is given in the following abstract. We are grateful to Leon Avery for setting up our CGC gopher server and also for arranging for the electronic submission of WBG abstracts (as well as abstracts for various C. elegans meetings). His C. elegans WWW server has become an essential resource for the worm community. We were therefore pleased to include Leon (only 5% effort) in a second subcontract as part of our new CGC application. We welcome comments and suggestions about any of the CGC activities.

Gleason, Ryan et al. (2013) International Worm Meeting "Disparate endocytic recycling of the TGFb signaling receptors, Sma-6 and Daf-4, regulates signaling of the Sma/Mab pathway."

Li, Ying, Padgett, Richard, Grant, Barth, Gleason, Ryan, Kane, Nanci, Akintobi, Adenrele (Dee)

[International Worm Meeting, 2013]

Our study aims to delineate the intracellular trafficking pathways that regulate the type I and type II TGFb receptors, Sma-6 and Daf-4 respectively. The TGFb superfamily of ligands regulate a diverse array of developmental processes across metazoan biology. Genetic and genomic analysis in C. elegans has contributed to the delineation of the highly conserved TGFb signal transduction pathway. An unanswered and critical question is how receptor-mediated endocytosis orchestrates the availability and intracellular trafficking (degradation versus recycling) of TGFb signaling receptors. By utilizing C. elegans we have identified a novel role of two distinct endocytic trafficking pathways in regulating both the recycling and signaling of the two TGFb receptors, Sma-6 and Daf-4. To test the receptor trafficking of the Sma/Mab pathway, functional translational fusions of both Sma-6 and Daf-4 were developed to various fluorescent proteins to assess the in vivo localization and availability of the receptors in genetically tractable endocytic mutants. Here we show that the protein sorting complex, the Retromer, is an essential linchpin in the decision to recycle or degrade Sma-6. In the absence of the Retromer complex Sma-6 is not recycled back to the Plasma membrane and is mis-sorted to the Lysosome for degradation. In contrast, Daf-4 recycles through the recycling endosome and is not dependent on the Retromer complex. Co-IP experiments demonstrate a direct interaction between the Retromer complex and Sma-6. Together, this work establishes a novel role for disparate intracellular trafficking in the regulation of TGFb receptor availability and signaling.

Kelley S (2000) Brief Bioinform "Getting started with Acedb."

Kelley S

[Brief Bioinform, 2000]

Acedb is one of the more venerable pieces of Genomics software. Acedb was originally created in 1992 by Richard Durbin and Jean Thierry-Mieg to manage the data from the Caenorhabditis elegans mapping project and subsequently the C. elegans sequencing project. From beginnings as a C. elegans-specific tool, it has been continuously developed into a flexible suite of data management, display and scripting tools providing facilities for managing and annotation mapping information and DNA and peptide sequences.This paper gives a basic overview of the Acedb suite, and step-by-step guidance on how to download and install Acedb. It is intended to take an Acedb novice to stage where they can begin to experiment and explore the facilities that are available.