Phosphatidylinositol transfer protein-α in netrin-1-induced PLC signalling and neurite outgrowth

Xie, Yi; Ding, Yu; Hong, Yan; Zhu, Feng; Navarre, Sammy; Xi, Cai Xia; Zhu, Xinen; Wang, C. L.; Ackerman, Susan L.; Kozlowski, David J.; Mei, Lin; Xiong, Wen Cheng

doi:10.1038/ncb1321

Cited by 87 publications

(74 citation statements)

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“…Several signaling pathways are activated by netrin signaling through DCC/UNC40 family members, although neogenin is understudied compared with its mammalian paralogue DCC (Forcet et al, 2002;Campbell and Holt, 2003;Li et al, , 2008Liu et al, 2004;Ren et al, 2004;Xie et al, 2005;Zhu et al, 2007). Both FAK and ERK are activated by, and required for, netrin-1/DCC signaling in axon guidance (Forcet et al, 2002;Campbell and Holt, 2003;Li et al, 2004;Liu et al, 2004;Ren et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Netrin-1 treatment of neurons also leads to DCC-dependent activation of ERK mitogen-activated protein kinase (MAPK) and inhibition of ERK signaling blocks neurite outgrowth and growth cone turning in response to a netrin gradient in vitro (Forcet et al, 2002;Campbell and Holt, 2003). Additional signaling pathways are also activated by netrin-1 signaling via DCC and neogenin (Xie et al, 2005;Zhu et al, 2007;Li et al, 2008).Although neogenin and DCC are similar in their signaling responses to netrin-1 (although not identical, see Xie et al, 2006;Ren et al, 2008), neogenin plays a broader role in development than DCC. First, neogenin, but not DCC, binds to members of a second family of ligands, the GPI-anchored repulsive guidance molecules (RGMa, RGMb, and RGMc) (Rajagopalan et al, 2004;Zhang et al, 2005).…”

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Neogenin Regulates Skeletal Myofiber Size and Focal Adhesion Kinase and Extracellular Signal-regulated Kinase Activities In Vivo and In Vitro

Bae

Yang

Jiang

et al. 2009

MBoC

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A variety of signaling pathways participate in the development of skeletal muscle, but the extracellular cues that regulate such pathways in myofiber formation are not well understood. Neogenin is a receptor for ligands of the netrin and repulsive guidance molecule (RGM) families involved in axon guidance. We reported previously that neogenin promoted myotube formation by C2C12 myoblasts in vitro and that the related protein Cdo (also Cdon) was a potential neogenin coreceptor in myoblasts. We report here that mice homozygous for a gene-trap mutation in the Neo1 locus (encoding neogenin) develop myotomes normally but have small myofibers at embryonic day 18.5 and at 3 wk of age. Similarly, cultured myoblasts derived from such animals form smaller myotubes with fewer nuclei than myoblasts from control animals. These in vivo and in vitro defects are associated with low levels of the activated forms of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK), both known to be involved in myotube formation, and inefficient expression of certain muscle-specific proteins. Recombinant netrin-2 activates FAK and ERK in cultured myoblasts in a neogenin-and Cdo-dependent manner, whereas recombinant RGMc displays lesser ability to activate these kinases. Together, netrin-neogenin signaling is an important extracellular cue in regulation of myogenic differentiation and myofiber size. INTRODUCTIONSkeletal muscle is the most abundant tissue, by mass, in the vertebrate body. Muscles of the trunk and limbs arise from the somites, with myogenic progenitor cells derived from the dorsal region of the maturing somite, the dermomyotome (Tajbakhsh and Buckingham, 2000;Pownall et al., 2002;Charge and Rudnicki, 2004). In response to signals from the adjacent notochord, neural tube, and surface ectoderm, some dermomyotomal progenitors become committed to the muscle lineage and form the myotome, a set of differentiated muscle cells that underlies the dermomyotome. Subsequent embryonic, fetal, and postnatal stages of myogenesis are thought to involve additional muscle progenitors that migrate from the dermomyotome and ultimately establish the trunk and limb musculature, as well as satellite cells, adult muscle precursor cells (Gros et al., 2005;Kassar-Duchossoy et al., 2005;Relaix et al., 2005). Somitic progenitor cells are specified to become muscle lineage-committed myoblasts through the action of the myogenic basic helix-loop-helix transcription factors Myf5, MRF4, and MyoD, whereas differentiation of myoblasts is regulated by myogenin, MyoD, and MRF4 (Tajbakhsh, 2005). These and other transcription factors coordinate the process of differentiation, including cell cycle withdrawal, expression of muscle-specific proteins, cellular elongation, and fusion into multinucleated myofibers. Although transcriptional regulation is at the core of myogenesis, the formation and growth of myofibers is also controlled by a variety of signaling ligands and their receptors, including insulin-like growth factor-1, fibroblast growth fac...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Neogenin Regulates Skeletal Myofiber Size and Focal Adhesion Kinase and Extracellular Signal-regulated Kinase Activities In Vivo and In Vitro

Bae

Yang

Jiang

et al. 2009

MBoC

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“…Altered levels of sphingomyelin, ceramides, and cholesterol esters, and altered expression of genes involved in the control of lipid metabolism have been identified in the spinal cord of ALS patients and transgenic SOD1-ALS mice (Malaspina et al, 2001;Cutler et al, 2002). In addition, mice with a targeted disruption in the liver X receptor ␤, a ubiquitous sterol-activated nuclear receptor involved in cholesterol and sterol metabolism, exhibit degenerative changes in motor neurons and muscle atrophy reminiscent of ALS (Andersson et al, 2005;Xie et al, 2005). Furthermore, plant and bacterial sterol derivatives have been shown to be neurotoxic, and have been linked to the pathogenesis of the Guam ALSparkinsonism dementia complex (Ly et al, 2007) In sum, we hypothesize that the combination of loss of function (disrupted FFAT-motif binding), dominant-negative effects (wild-type VAP recruitment), and gain of toxic function (disrupted membrane trafficking) may lead to VAPB-linked motor neuron disease.…”

Section: Model Of Vap Leading To Motor Neuron Degenerationmentioning

confidence: 99%

Motor Neuron Disease-Associated Mutant Vesicle-Associated Membrane Protein-Associated Protein (VAP) B Recruits Wild-Type VAPs into Endoplasmic Reticulum-Derived Tubular Aggregates

Teuling¹,

Ahmed²,

Haasdijk³

et al. 2007

J. Neurosci.

215

310

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The vesicle-associated membrane protein-associated proteins (VAPs) VAPA and VAPB interact with lipid-binding proteins carrying a short motif containing two phenylalanines in an acidic tract (FFAT motif) and targets them to the cytosolic surface of the endoplasmic reticulum (ER). A genetic mutation (P56S) in the conserved major sperm protein homology domain of VAPB has been linked to motorneuron degeneration in affected amyotrophic lateral sclerosis (ALS) patients. We report that in the CNS, VAPB is abundant in motor neurons and that the P56S substitution causes aggregation of mutant VAPB in immobile tubular ER clusters, perturbs FFAT-motif binding, and traps endogenous VAP in mutant aggregates. Expression of mutant VAPB or reduction of VAP by short hairpin RNA in primary neurons causes Golgi dispersion and cell death. VAPA and VAPB are reduced in human ALS patients and superoxide dismutase 1 (SOD1)-ALS-transgenic mice, suggesting that VAP family proteins may be involved in the pathogenesis of sporadic and SOD1-linked ALS. Our data support a model in which reduced levels of VAP family proteins result in decreased ER anchoring of lipid-binding proteins and cause motor neuron degeneration.

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“…The binding of netrin 1 to DCC also promotes the synthesis of the phosphoinositide phosphatidylinositol (4,5) bisphosphate (PIP 2 ) (Xie et al, 2005), which is phosphorylated by phosphatidylinositol-3 kinase (PI3K) and results in phosphatidylinositol (3,4,5) trisphosphate (PIP 3 ) production. Notably, PIP 3 facilitates the binding of GTPases to their effectors, thereby enhancing signalling (Di Paolo and De Camilli, 2006).…”

Section: Chemoattractant Signal Transduction Cascadesmentioning

confidence: 99%

Netrins: versatile extracellular cues with diverse functions

2011

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SummaryNetrins are secreted proteins that were first identified as guidance cues, directing cell and axon migration during neural development. Subsequent findings have demonstrated that netrins can influence the formation of multiple tissues, including the vasculature, lung, pancreas, muscle and mammary gland, by mediating cell migration, cell-cell interactions and cell-extracellular matrix adhesion. Recent evidence also implicates the ongoing expression of netrins and netrin receptors in the maintenance of cell-cell organisation in mature tissues. Here, we review the mechanisms involved in netrin signalling in vertebrate and invertebrate systems and discuss the functions of netrin signalling during the development of neural and non-neural tissues.Key words: DCC, Adhesion, Axon, Neogenin, Netrin, UNC5 IntroductionNetrins are a family of extracellular, laminin-related (see Glossary, Box 1) proteins that function as chemotropic guidance cues for migrating cells and axons during neural development. They act as chemoattractants for some cell types and chemorepellents for others. Loss-of-function mutations in netrin 1 or in certain netrin receptors are lethal in mice, highlighting the importance of netrin signalling during development. Insights into the functions of netrins have arisen from studies across a wide range of animal species, including invertebrates such as the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster, non-mammalian vertebrates such as the frog Xenopus laevis, and mammals including rats, mice and humans.Since its discovery in the early 1990s, it is now becoming clear that the netrin gene family exhibits a rich biology, with significance beyond neural development, and contributes to the organisation of multiple tissues. Along with a number of other identified axon guidance cues (Hinck, 2004), secreted netrins influence organogenesis outside the central nervous system (CNS), directing cell migration and mediating cell-cell adhesion in the lung, pancreas, mammary gland, vasculature and muscle (Kang et al., 2004; Lejmi et al., 2008;Liu et al., 2004;Lu et al., 2004;Srinivasan et al., 2003;Yebra et al., 2003). Here, we discuss the cell biology of netrin and netrin receptor functions and review the downstream signal transduction mechanisms that they activate. We also provide an overview of netrin function during development, both within the nervous system and within other developing organs and tissues. Netrin family membersThe first reported member of the netrin family, uncoordinated-6 (UNC-6), was identified in a search for gene products that regulate neural development in C. elegans (Ishii et al., 1992). Netrins have since been identified and studied in multiple vertebrate and invertebrate species (Table 1), including X. laevis (de la Torre et al., 1997), D. melanogaster (Harris et al., 1996;Mitchell et al., 1996) and the sea anemone Nematostella vectensis (Matus et al., 2006), an animal that exhibits early hallmarks of the origins of bilateral symmetry. In mammals, three...

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Phosphatidylinositol transfer protein-α in netrin-1-induced PLC signalling and neurite outgrowth

Cited by 87 publications

References 35 publications

Neogenin Regulates Skeletal Myofiber Size and Focal Adhesion Kinase and Extracellular Signal-regulated Kinase Activities In Vivo and In Vitro

Neogenin Regulates Skeletal Myofiber Size and Focal Adhesion Kinase and Extracellular Signal-regulated Kinase Activities In Vivo and In Vitro

Motor Neuron Disease-Associated Mutant Vesicle-Associated Membrane Protein-Associated Protein (VAP) B Recruits Wild-Type VAPs into Endoplasmic Reticulum-Derived Tubular Aggregates

Netrins: versatile extracellular cues with diverse functions

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