Function of the<i>Drosophila</i>receptor guanylyl cyclase Gyc76C in PlexA-mediated motor axon guidance

Chak, Kayam; Kolodkin, Alex L.

doi:10.1242/dev.095968

Cited by 15 publications

(17 citation statements)

References 64 publications

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“…The L635H missense mutation in gyc76C 3L043 alters a residue within the PTKc domain that is conserved in vertebrate NPRs ( Fig 2C ). However, the Gyc76C PTKc domain, like that of the NPRs, lacks a glutamate that is required to catalyze phosphate transfer and thus is likely kinase dead [ 60 ]; this domain is thought to regulate the activity of the guanylyl cyclase domain [ 39 , 59 ].…”

Section: Resultsmentioning

confidence: 99%

“…melanogaster [ 31 – 33 ]. Gyc76C has been previously characterized for its role in Semaphorin-mediated axon guidance; Malpighian tubule physiology, and the development of embryonic muscles and salivary glands [ 34 – 39 ]. Like the similar mammalian natriuretic peptide receptors NPR1 and NPR2 [ 40 ], the guanylyl cyclase activity of Gyc76C is likely regulated by secreted peptides [ 35 ], and can act via a variety of downstream cGMP sensors.…”

Section: Introductionmentioning

confidence: 99%

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The Gyc76C Receptor Guanylyl Cyclase and the Foraging cGMP-Dependent Kinase Regulate Extracellular Matrix Organization and BMP Signaling in the Developing Wing of Drosophila melanogaster

Schleede

Blair

2015

PLoS Genet

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The developing crossveins of the wing of Drosophila melanogaster are specified by long-range BMP signaling and are especially sensitive to loss of extracellular modulators of BMP signaling such as the Chordin homolog Short gastrulation (Sog). However, the role of the extracellular matrix in BMP signaling and Sog activity in the crossveins has been poorly explored. Using a genetic mosaic screen for mutations that disrupt BMP signaling and posterior crossvein development, we identify Gyc76C, a member of the receptor guanylyl cyclase family that includes mammalian natriuretic peptide receptors. We show that Gyc76C and the soluble cGMP-dependent kinase Foraging, likely linked by cGMP, are necessary for normal refinement and maintenance of long-range BMP signaling in the posterior crossvein. This does not occur through cell-autonomous crosstalk between cGMP and BMP signal transduction, but likely through altered extracellular activity of Sog. We identify a novel pathway leading from Gyc76C to the organization of the wing extracellular matrix by matrix metalloproteinases, and show that both the extracellular matrix and BMP signaling effects are largely mediated by changes in the activity of matrix metalloproteinases. We discuss parallels and differences between this pathway and other examples of cGMP activity in both Drosophila melanogaster and mammalian cells and tissues.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Gyc76C Receptor Guanylyl Cyclase and the Foraging cGMP-Dependent Kinase Regulate Extracellular Matrix Organization and BMP Signaling in the Developing Wing of Drosophila melanogaster

Schleede

Blair

2015

PLoS Genet

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“…In Drosophila , class A plexin forms a holo-receptor with the receptor guanylyl cyclase Gyc76C, which binds GIPC1 and facilitates plexin-mediated motor axon guidance (Chak and Kolodkin, 2014). GIPCs therefore can use diverse mechanisms to regulate plexin signaling.…”

Section: Discussionmentioning

confidence: 99%

Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex

Shang

Brautigam

Chen

et al. 2017

eLife

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The GIPC family adaptor proteins mediate endocytosis by tethering cargo proteins to the myosin VI motor. The structural mechanisms for the GIPC/cargo and GIPC/myosin VI interactions remained unclear. PlexinD1, a transmembrane receptor that regulates neuronal and cardiovascular development, is a cargo of GIPCs. GIPC-mediated endocytic trafficking regulates PlexinD1 signaling. Here, we unravel the mechanisms of the interactions among PlexinD1, GIPCs and myosin VI by a series of crystal structures of these proteins in apo or bound states. GIPC1 forms a domain-swapped dimer in an autoinhibited conformation that hinders binding of both PlexinD1 and myosin VI. PlexinD1 binding to GIPC1 releases the autoinhibition, promoting its interaction with myosin VI. GIPCs and myosin VI interact through two distinct interfaces and form an open-ended alternating array. Our data support that this alternating array underlies the oligomerization of the GIPC/Myosin VI complexes in solution and cells.DOI: http://dx.doi.org/10.7554/eLife.27322.001

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“…Semi-transparency of Class V semaphorin Ig and PSI domains indicates that these domains are present in some, but not all, viral semaphorins. Sema (semaphorin domain), PSI (plexin-semaphorin-integrin domain), Ig (immunoglobulin domain), Basic (basic domain), PDZ (PDZ domain), TSP (Thrombospondin domain), GPI (glycosylphosphatidylinositol linkage), RTK (receptor tyrosine kinase), Npn1 (Neuropilin 1), Npn2 (Neuropilin 2), CAM (cell adhesion molecule) Tim-2 (T-cell Ig and mucin domain containing protein 2), CD72 (B cell differentiation antigen CD72), CLCP1 (CUB, LCCL-homology, Coagulation factor V/VIII homology domains protein 1), TREM2 (Triggering Receptor Expressed on Myeloid Cells 2), DAP12 (DNAX activating protein of 12 kDa)((1,12,23,46,232,233) and references therein.…”

Section: Figurementioning

confidence: 99%

Semaphorins and their Signaling Mechanisms

Alto

Terman

2016

Methods in Molecular Biology

294

245

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Semaphorins are extracellular signaling proteins that are essential for the development and maintenance of many organs and tissues. The more than 20-member semaphorin protein family includes secreted, transmembrane and cell surface-attached proteins with diverse structures, each characterized by a single cysteine-rich extracellular sema domain, the defining feature of the family. Early studies revealed that semaphorins function as axon guidance molecules, but it is now understood that semaphorins are key regulators of morphology and motility in many different cell types including those that make up the nervous, cardiovascular, immune, endocrine, hepatic, renal, reproductive, respiratory and musculoskeletal systems, as well as in cancer cells. Semaphorin signaling occurs predominantly through Plexin receptors and results in changes to the cytoskeletal and adhesive machinery that regulate cellular morphology. While much remains to be learned about the mechanisms underlying the effects of semaphorins, exciting work has begun to reveal how semaphorin signaling is fine-tuned through different receptor complexes and other mechanisms to achieve specific outcomes in various cellular contexts and physiological systems. These and future studies will lead to a more complete understanding of semaphorin-mediated development and to a greater understanding of how these proteins function in human disease.

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Function of theDrosophilareceptor guanylyl cyclase Gyc76C in PlexA-mediated motor axon guidance

Cited by 15 publications

References 64 publications

The Gyc76C Receptor Guanylyl Cyclase and the Foraging cGMP-Dependent Kinase Regulate Extracellular Matrix Organization and BMP Signaling in the Developing Wing of Drosophila melanogaster

The Gyc76C Receptor Guanylyl Cyclase and the Foraging cGMP-Dependent Kinase Regulate Extracellular Matrix Organization and BMP Signaling in the Developing Wing of Drosophila melanogaster

Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex

Semaphorins and their Signaling Mechanisms

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