Type IV Collagen Is Detectable in Most, but Not All, Basement Membranes of <i>Caenorhabditis elegans</i> and Assembles on Tissues That Do Not Express It

Graham, Patricia L.; Johnson, James E.; Wang, Shaoru; Sibley, Marion H.; Gupta, Malini C.; Kramer, James M.

doi:10.1083/jcb.137.5.1171

Cited by 125 publications

(116 citation statements)

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“…EMB-9 is a basement membrane collagen (Graham et al 1997). The NSM neurosecretory neurons release serotonin directly onto a basement membrane surrounding the pharynx, so the serotonin must traverse the basement membrane to reach target cells outside the pharynx (Axäng et al 2008).…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…We note, however, that we isolated an abts-1 mutant in a screen performed using the mod-5 mutant background, and we have not detected any effect of abts-1 mutations on serotonin response in a wildtype background (data not shown). FLP-1 is a neuropeptide previously known to affect serotonin response (Nelson et al 1998), ELPC-3 is the catalytic subunit of a lysine acetylase protein complex (Chen et al 2009;Solinger et al 2010), and EMB-9 is a collagen that is a component of basement membranes (Graham et al 1997).Our results suggest MOD-1 and SER-4 are serotonin receptors that inhibit C. elegans locomotion, and we propose that the other proteins detected in our genetic screens affect signaling by MOD-1 and/or SER-4. To lay the foundation for understanding of how all of the proteins mediate serotonin response, we first focused on how the two receptors affect locomotion.…”

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confidence: 99%

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Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion inCaenorhabditis elegans

et al. 2012

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A better understanding of the molecular mechanisms of signaling by the neurotransmitter serotonin is required to assess the hypothesis that defects in serotonin signaling underlie depression in humans. Caenorhabditis elegans uses serotonin as a neurotransmitter to regulate locomotion, providing a genetic system to analyze serotonin signaling. From large-scale genetic screens we identified 36 mutants of C. elegans in which serotonin fails to have its normal effect of slowing locomotion, and we molecularly identified eight genes affected by 19 of the mutations. Two of the genes encode the serotonin-gated ion channel MOD-1 and the G-protein-coupled serotonin receptor SER-4. mod-1 is expressed in the neurons and muscles that directly control locomotion, while ser-4 is expressed in an almost entirely non-overlapping set of sensory and interneurons. The cells expressing the two receptors are largely not direct postsynaptic targets of serotonergic neurons. We analyzed animals lacking or overexpressing the receptors in various combinations using several assays for serotonin response. We found that the two receptors act in parallel to affect locomotion. Our results show that serotonin functions as an extrasynaptic signal that independently activates multiple receptors at a distance from its release sites and identify at least six additional proteins that appear to act with serotonin receptors to mediate serotonin response. DEPRESSION is hypothesized to involve dysfunction of the neurotransmitter serotonin (Cowen 2008). Understanding the molecular mechanism of serotonin signaling is complicated by the fact that the human brain expresses 14 types of serotonin receptors, one of which is a serotonin-gated ion channel, and the rest of which are G-protein-coupled receptors (Millan et al. 2008). An additional challenge to understanding serotonin signaling is the fact that serotonin can act locally at synapses where it is released or diffuse away and act at distant receptors. While classical neurotransmitters such as GABA and glutamate appear to function mainly locally at synapses, serotonin can diffuse several microns from its release sites at concentrations sufficient to activate its receptors (Bunin and Wightman 1998). Furthermore, serotonin receptors are often localized at nonsynaptic sites (Kia et al. 1996). These observations suggest that serotonin might act predominantly as an extrasynaptic signal to activate several receptor types on cells distant from its release sites and that the combined action of these several receptors somehow coordinates appropriate responses to serotonin. The details of how such action might occur remain unclear.Caenorhabditis elegans uses serotonin as a neurotransmitter (Horvitz et al. 1982;Chase and Koelle 2007) and provides a model system with the potential to make important contributions to the study of serotonin signaling. First, C. elegans allows the use of forward genetic screens to identify the proteins beyond serotonin receptors that mediate serotonin response. Second, the known...

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Section: Discussionmentioning

confidence: 99%

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Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion inCaenorhabditis elegans

et al. 2012

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“…Frozen sections were prepared as described (39). After blocking the sections with 0.1% (wt/vol) Triton X-100 and 3% BSA in PBS, they were immunostained by incubation with anti-LET-2 (NW68, 1:200) (14), mouse anti-GFP IgG (3E6, 1:200; Molecular Probes), mouse monoclonal anti-DAF-21(HSP90) (608F, 1:10) (40), anti-NID-1 (5 g/ml) or rat anti-HA IgG (3F10, 2 g/ml; Roche) for 12 h at 4°C followed by incubation with the appropriate Alexa Fluor-conjugated secondary Ab (1:500; Molecular Probes) for 1 h at room temperature and then stained with DAPI (2 g/ml; Wako) for 10 min at room temperature. Anti-NID-1 was preabsorbed with the acetone powder of nid-1(cg119) null mutants.…”

Section: Methodsmentioning

confidence: 99%

MIG-17/ADAMTS controls cell migration by recruiting nidogen to the basement membrane in C. elegans

Kubota¹,

Ohkura

Tamai

et al. 2008

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

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Mutations in the a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) family of secreted proteases cause diseases linked to ECM abnormalities. However, the mechanisms by which these enzymes modulate the ECM during development are mostly unexplored. The Caenorhabditis elegans MIG-17/AD-AMTS protein is secreted from body wall muscle cells and localizes to the basement membrane (BM) of the developing gonad where it controls directional migration of gonadal leader cells. Here we show that specific amino acid changes in the ECM proteins fibulin-1C (FBL-1C) and type IV collagen (LET-2) result in bypass of the requirement for MIG-17 activity in gonadal leader cell migration in a nidogen (NID-1)-dependent and -independent manner, respectively. The MIG-17, FBL-1C and LET-2 activities are required for proper accumulation of NID-1 at the gonadal BM. However, mutant FBL-1C or LET-2 in the absence of MIG-17 promotes NID-1 localization. Furthermore, overexpression of NID-1 in mig-17 mutants substantially rescues leader cell migration defects. These results suggest that functional interactions among BM molecules are important for MIG-17 control of gonadal leader cell migration. We propose that FBL-1C and LET-2 act downstream of MIG-17-dependent proteolysis to recruit NID-1 and that LET-2 also activates a NID-1-independent pathway, thereby inducing the remodeling of the BM required for directional control of leader cell migration.ECM ͉ fibulin-1 ͉ organogenesis ͉ type IV collagen T he interaction between basement membranes (BMs) and migrating cells or the epithelial layer is a complicated but carefully controlled process that involves remodeling of the ECM. For example, the migration of border cells required for oogenesis and patterning of the early embryo in Drosophila melanogaster is accompanied by precise regulation of the synthesis and degradation of type IV collagen, laminin, and perlecan (1, 2). Fibronectin expression is required for branching morphogenesis of the submandibular salivary gland, lung, and kidney in mouse (3). However, the mechanisms of cell-ECM interactions and the roles of BMs in cell migration remain largely unknown.Gonadogenesis in the nematode Caenorhabditis elegans serves as a simple model system for elucidating the function of BMs in organ morphogenesis. The development of hermaphrodite gonads is regulated by the migration of gonadal distal tip cells (DTCs), which promote directional elongation of the gonad arms during the larval stages to form the U-shaped gonads found in adult animals (4, 5). Two secreted a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) family metalloproteases, MIG-17 and GON-1, are involved in this process. GON-1 is required for DTC motility, whereas MIG-17 controls the direction of DTC movement but does not control DTC motility per se (6, 7). MIG-17 is expressed in the body wall muscles and is localized to the BM of the gonad surface, where it is required for DTC migration (7,8). It has been proposed that MIG-17 and GON-1 remodel BMs via prote...

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“…Activation changes the structure of specific domains and results in increased homophilic interactions or heterophilic interactions with other ECM proteins as molecules assemble into higher order structures. Hemicentin is secreted from lateral muscle and gonad leader cells into the pseudocolemic cavity and, like type IV collagen, is re-Hemicentin functions in C. elegans 876 npg cruited by an unknown mechanism to diverse cell surfaces where it assembles into polymers [3,15]. The amino-terminal VWA domain is sufficient to target hemicentin to cell surfaces, and the metal ion-dependent adhesion site within the VWA domain is necessary for targeting function ( [16], see Figure 1).…”

Section: Hemicentin Assemblymentioning

confidence: 99%

Hemicentins: What have we learned from worms?

et al. 2006

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npg Hemicentins are conserved extracellular matrix proteins discovered in Caenorhabditis elegans, with orthologs in all vertebrate species including human and mouse. Hemicentins share a single, highly conserved amino-terminal von Willebrand A domain, followed by a long (>40) stretch of immunoglobulin repeats, multiple tandem epidermal growth factors and a fibulin-like carboxy-terminal module. C. elegans has a single hemicentin gene that has pleiotropic functions in transient cell contacts that are required for cell migration and basement membrane invasion and in stable contacts at hemidesmosome-mediated cell junctions and elastic fiber-like structures. Here, we summarize what is known about the function of hemicentin in C. elegans and discuss implications for hemicentin function in other species.

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Type IV Collagen Is Detectable in Most, but Not All, Basement Membranes of Caenorhabditis elegans and Assembles on Tissues That Do Not Express It

Cited by 125 publications

References 70 publications

Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion inCaenorhabditis elegans

Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion inCaenorhabditis elegans

MIG-17/ADAMTS controls cell migration by recruiting nidogen to the basement membrane in C. elegans

Hemicentins: What have we learned from worms?

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