The RGM protein DRAG-1 positively regulates a BMP-like signaling pathway in<i>Caenorhabditis elegans</i>

Tian, Chenxi; Sen, Debjeet; Shi, Herong; Foehr, Marisa L.; Plavskin, Yevgeniy; Vatamaniuk, Olena K.; Li, Jun

doi:10.1242/dev.051615

Cited by 45 publications

(96 citation statements)

References 60 publications

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“…This included analysis of a hypodermal expression of a concatamer of smad-binding elements driving GFP [the reporter acting downstream of SMAD (RAD-SMAD) reporter] and quantitative RT-PCR (qRT-PCR) analysis of transcript levels of two intestine-specific genes whose expression levels are regulated by the Sma/Mab pathway ( Fig. 1 G and H) (13)(14)(15).…”

Section: Clathrin-dependent Endocytosis Is Necessary For Bmp Receptormentioning

confidence: 99%

BMP signaling requires retromer-dependent recycling of the type I receptor

Gleason

Akintobi²,

Grant³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

105

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The transforming growth factor β (TGFβ) superfamily of signaling pathways, including the bone morphogenetic protein (BMP) subfamily of ligands and receptors, controls a myriad of developmental processes across metazoan biology. Transport of the receptors from the plasma membrane to endosomes has been proposed to promote TGFβ signal transduction and shape BMP-signaling gradients throughout development. However, how postendocytic trafficking of BMP receptors contributes to the regulation of signal transduction has remained enigmatic. Here we report that the intracellular domain of Caenorhabditis elegans BMP type I receptor SMA-6 (small-6) binds to the retromer complex, and in retromer mutants, SMA-6 is degraded because of its missorting to lysosomes. Surprisingly, we find that the type II BMP receptor, DAF-4 (dauer formation-defective-4), is retromer-independent and recycles via a distinct pathway mediated by ARF-6 (ADP-ribosylation factor-6). Importantly, we find that loss of retromer blocks BMP signaling in multiple tissues. Taken together, our results indicate a mechanism that separates the type I and type II receptors during receptor recycling, potentially terminating signaling while preserving both receptors for further rounds of activation.endocytosis | receptor trafficking | C. elegans

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Section: Clathrin-dependent Endocytosis Is Necessary For Bmp Receptormentioning

confidence: 99%

BMP signaling requires retromer-dependent recycling of the type I receptor

Gleason

Akintobi²,

Grant³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

105

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“…Hermaphrodites carrying the RAD-SMAD reporter jjIs2437 II (Tian et al, 2010) were treated with hypochlorite. The resulting embryos were allowed to hatch in M9 buffer at 16°C.…”

Section: Rad-smad Reporter Assaymentioning

confidence: 99%

“…Animal fixation, immunostaining, microscopy and image analysis were performed as described previously (Tian et al, 2010). Guinea pig anti-FOZI-1 (1:200) (Amin et al, 2007), mouse monoclonal anti-AJM-1 MH27 (1:100; Developmental Studies Hybridoma Bank, University of Iowa), rat anti-MLS-2 (1:200) (Jiang et al, 2005) and goat anti-GFP (1:1000; Rockland Immunochemicals) were used.…”

Section: Immunofluorescence Stainingmentioning

confidence: 99%

The neogenin/DCC homolog UNC-40 promotes BMP signaling via the RGM protein DRAG-1 in C. elegans

et al. 2013

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The deleted in colorectal cancer (DCC) homolog neogenin functions in both netrin- and repulsive guidance molecule (RGM)-mediated axon guidance and in bone morphogenetic protein (BMP) signaling. How neogenin functions in mediating BMP signaling is not well understood. We show that the sole C. elegans DCC/neogenin homolog UNC-40 positively modulates a BMP-like pathway by functioning in the signal-receiving cells at the ligand/receptor level. This function of UNC-40 is independent of its role in netrin-mediated axon guidance, but requires its association with the RGM protein DRAG-1. We have identified the key residues in the extracellular domain of UNC-40 that are crucial for UNC-40-DRAG-1 interaction and UNC-40 function. Surprisingly, the extracellular domain of UNC-40 is sufficient to promote BMP signaling, in clear contrast to the requirement of its intracellular domain in mediating axon guidance. Mouse neogenin lacking the intracellular domain is also capable of mediating BMP signaling. These findings reveal an unexpected mode of action for neogenin regulation of BMP signaling.

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“…To further assess the training effect on DBL-1 signaling, we examined the downstream activity in the hypodermis, the target tissue of DBL-1 in aversive olfactory learning, using a gfp reporter of DBL-1 activity, RAD-SMAD (39). RAD-SMAD expression is positively regulated by DBL-1 and is found in multiple tissues, including the intestine and hypodermis (39).…”

Section: Dbl-1 Signals To the Hypodermis To Direct Aversive Olfactorymentioning

confidence: 99%

“…RAD-SMAD expression is positively regulated by DBL-1 and is found in multiple tissues, including the intestine and hypodermis (39). We quantified RAD-SMAD level in the hypodermis of transgenic animals that expressed DBL-1 only in AVA neurons in the dbl-1(nk3) background.…”

Section: Dbl-1 Signals To the Hypodermis To Direct Aversive Olfactorymentioning

confidence: 99%

DBL-1, a TGF-β, is essential for Caenorhabditis elegans aversive olfactory learning

Zhang¹,

Zhang

2012

Proc. Natl. Acad. Sci. U.S.A.

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The TGF-β superfamily is conserved throughout metazoan, and its members play essential roles in development and disease. TGF-β has also been implicated in adult neural plasticity. However, the underlying mechanisms are not well understood. Here we report that DBL-1, a Caenorhabditis elegans TGF-β homolog known to control body morphology and immunity, is essential for aversive olfactory learning of potentially harmful bacteria food. We show that DBL-1 generated by the AVA command interneurons, which are critical for sensorimotor responses, regulates aversive olfactory learning, and that the activity of the type I TGF-β receptor SMA-6 in the hypodermis is needed during adulthood to generate olfactory plasticity. These spatial and temporal mechanisms are critical for the DBL-1 signaling to achieve its diverse functions in development and adult neural plasticity. Interestingly, aversive training decreases AVA calcium response, leading to an increase in the DBL-1 signal secreted from AVA, revealing an experience-dependent change that can underlie the role of TGF-β signaling in mediating plasticity.experience-dependent secretion | molecular and cellular mechanisms for TGF-beta pathway in learning

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The RGM protein DRAG-1 positively regulates a BMP-like signaling pathway inCaenorhabditis elegans

Cited by 45 publications

References 60 publications

BMP signaling requires retromer-dependent recycling of the type I receptor

BMP signaling requires retromer-dependent recycling of the type I receptor

The neogenin/DCC homolog UNC-40 promotes BMP signaling via the RGM protein DRAG-1 in C. elegans

DBL-1, a TGF-β, is essential for Caenorhabditis elegans aversive olfactory learning

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