Sema4D, the Ligand for Plexin B1, Suppresses c-Met Activation and Migration and Promotes Melanocyte Survival and Growth

Soong, Joanne; Chen, Yulin; Shustef, Elina; Scott, Glynis

doi:10.1038/jid.2011.414

Cited by 45 publications

(45 citation statements)

References 48 publications

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“…Paracrine and autocrine factors regulate melanocyte function and play a role in transformation of melanocytes to melanoma (Haass et al, 2004;Villanueva and Herlyn, 2008). We have shown that melanocytes express the neural guidance receptor Plexin B1, which regulates melanocyte survival and proliferation, through binding to its ligand, Semaphorin 4D (Sema4D) (Soong et al, 2012). Sema4D is expressed by keratinocytes and melanocytes, thereby functioning as an autocrine and paracrine factor (Soong et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Plexin B1 inhibits MET through direct association and regulates Shp2 expression in melanocytes

Soong

Scott

2013

Journal of Cell Science

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SummaryPlexin B1, the receptor for Semaphorin 4D (Sema4D), is expressed by melanocytes in the skin. We recently showed that Sema4D suppresses activation of the hepatocyte growth factor receptor, MET, in melanocytes, and that knockdown of Plexin B1 results in activation of MET. MET signaling mediates proliferation, survival and migration in melanocytes, and its activation is associated with transformation of melanocytes to melanoma. In this report we investigated the mechanism by which Plexin B1 inhibits MET activation. Our results show that Plexin B1 and MET exist as an oligomeric receptor-receptor complex in melanocytes, and that receptor association is increased by Sema4D. MET and Plexin B1 receptor complexes were identified along the cell body of melanocytes, and Sema4D increased receptor association on dendrites, suggesting that Sema4D regulates MET-dependent processes at precise locations on the melanocyte. Despite activation of MET, Plexin B1 knockdowns proliferated slowly and showed increased apoptosis compared with controls. Shp2, a non-receptor protein tyrosine phosphatase, translates growth and survival signals from MET and other receptor tyrosine kinases. Plexin B1 knockdowns had markedly lower levels of Shp2 compared with controls, and Sema4D upregulated Shp2 expression at the protein and message level in normal melanocytes. Functional studies showed that blockade of Shp2 activity abrogated METdependent activation of Erk1/Erk2 and Akt in melanocytes. These results suggest a complex role for Sema4D and Plexin B1 in orchestrating signaling from the MET receptor in melanocytes. Because Shp2 is a downstream adaptor protein for multiple receptors, Sema4D may control the effects of several growth factors on melanocytes through regulation of Shp2.

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Section: Introductionmentioning

confidence: 99%

Plexin B1 inhibits MET through direct association and regulates Shp2 expression in melanocytes

Soong

Scott

2013

Journal of Cell Science

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“…Muitos trabalhos têm estudado o papel de CD100 no sistema nervoso (MOREAU-FAUVARQUE et al, 2003, YAMAGUCHI et al, 2011, em crescimento e angiogênese tumorais (BASILE et al, 2006, SIERRA et al, 2008, CH'NG e KUMANOGOH, 2010, GABROVSKA et al, 2011, SOONG et al, 2011, YANG et al, 2011 e em osteogênese. No sistema nervoso central foi demonstrado que CD100, em cérebro embrionário de camundongos, induz um colapso dos cones de crescimento de axônios (FURUYAMA et al, 1996, SWIERCZ et al, 2002, em cérebro pós-natal inibe o desenvolvimento de oligodendrócitos (YAMAGUCHI et al, 2011) e em adultos é expresso por oligodendrócitos e mielina e após uma lesão no SNC inibe a regeneração axonal (MOREAU-FAUVARQUE et al, 2003).…”

Section: Cd100 Seus Receptores E O Sistema Imuneunclassified

“…De fato, camundongos CD100 e plexina B1 negativos mostraram um fenótipo de osteosclerose devido ao aumento da formação óssea (NEGISHI-KOGA et al, 2011). Em tumores, CD100 tem efeito de supressão da proliferação de melanoma (SOONG et al, 2011). CD100 expresso em queratinócitos ao se associar a seu receptor Plexina B1 expresso por melanócitos, promove a sobrevivência e proliferação dos melanócitos humanos na pele (SOONG et al, 2011).…”

Section: Cd100 Seus Receptores E O Sistema Imuneunclassified

“…Em tumores, CD100 tem efeito de supressão da proliferação de melanoma (SOONG et al, 2011). CD100 expresso em queratinócitos ao se associar a seu receptor Plexina B1 expresso por melanócitos, promove a sobrevivência e proliferação dos melanócitos humanos na pele (SOONG et al, 2011). Em resposta a irradiação UV melanócitos diminuem a expressão de Plexina B1.…”

Section: Cd100 Seus Receptores E O Sistema Imuneunclassified

“…Em resposta a irradiação UV melanócitos diminuem a expressão de Plexina B1. Isso resulta em uma maior atividade do receptor c-Met, ativado pelo fator de crescimento de hepatócitos (HGF) produzido por queratinócitos e fibroblastos, e perda da expressão de E-caderina, promovendo a migração de melanócitos e, potencialmente, a transformação em melanoma (SOONG et al, 2011). Em câncer de pâncreas foi demonstrado que CD100 expresso por linfócitos infiltrantes no tumor pode potencializar a capacidade de invasão e de metástase das células tumorais através da interação plexina B1 e CD100 (KATO et al, 2011 (ZHU et al, 2007).…”

Section: Cd100 Seus Receptores E O Sistema Imuneunclassified

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Análise da atividade de CD100 na modulação da ativação de macrófagos e sua infectividade por Leishmania (Leishmania) amazonensis.

Galuppo¹

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Leishmaniasis is caused by trypanosomatids of the genus Leishmania, which infect mainly macrophages. The disease can have cutaneous, mucocutaneous and visceral forms, and over 350 million people worldwide live at risk areas. The main factors that influence form and severity of the disease are the species of Leishmania and the host immune response. Studies based on infected animal models susceptible and resistant to Leishmania show how the immune system of hosts with different profiles affects the survival of the parasite. Considering the importance of macrophages in Leishmania´s infection and the potential role of CD100 in the modulation of macrophage activation, we postulated that this molecule may affect macrophage infectivity. CD100 is known to reduce migration and expression of inflammatory cytokines in human monocytes and dendritic cells, and is induced in macrophages by inflammatory stimuli. Based on these informations, our objectives are to analyze and compare the expression of CD100 on different types of macrophages from BALB/c and C57BL/6 mice lineages and the effects of this molecule in terms of macrophage activation and infectivity by L. amazonensis. We analyzed the expression of CD100 in resident peritoneal macrophages from both strains of mice and the results suggest that macrophages from BALB/c mice express more CD100 than macrophages from C57BL/6 animals. We have also shown that macrophages from both BALB/c and C57BL/6 mice decrease the expression of CD100 along the infection with Leishmania amazonensis promastigotes. Experiments were also performed to analyze the modulation of soluble CD100 (sCD100) over infection of macrophages from both strains. The results show that macrophages from BALB/c mice pre-treated for 24 hours with sCD100 have augmented infection rates in of 4 hours of incubation. When macrophages remained in contact with the sCD100 before, during and after infection, rates increase after 4 and 24 hours of infection. In macrophages from C57BL/6 mice pre-treated for 24 hours with sCD100 and incubated with sCD100 during the infection rates augment in 4 hours of incubation. When macrophages remained in contact with sCD100 throughout the infection, rates increase after 4 and 24 hours of infection. We can therefore conclude that CD100 is expressed by different macrophage types, that it may be related to modulation of Leishmania´s infection and that the infection itself reduces CD100 expression in macrophages.

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The Semaphorin 4D-RhoA-Akt Signal Cascade Regulates Enamel Matrix Secretion in Coordination With Cell Polarization During Ameloblast Differentiation

Otsu

Ida‐Yonemochi

Fujiwara

et al. 2016

Journal of Bone and Mineral Research

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During tooth development, oral epithelial cells differentiate into ameloblasts in order to form the most mineralized tissue in the vertebrate body: enamel. During this process, ameloblasts directionally secrete enamel matrix proteins and morphologically change from low columnar cells to polarized tall columnar cells, both of which are essential for the proper formation of enamel. In this study, we elucidated the molecular mechanism that integrates ameloblast function and morphology. Immunohistochemistry revealed that the restricted expression of semaphorin 4D (Sema4D) and RhoA activation status are closely associated with ameloblast differentiation in mouse incisors. In addition, in vitro gain-of-function and loss-of-function experiments demonstrated that Sema4D acts upstream of RhoA to regulate cell polarity and amelogenin expression via the Plexin B1/Leukemia-associated RhoGEF (LARG) complex during ameloblast differentiation. Experiments in transgenic mice demonstrated that expression of a dominant-negative form of RhoA in dental epithelium hindered ameloblast differentiation and subsequent enamel formation, as well as perturbing the establishment of polarized cell morphology and vectorial amelogenin expression. Finally, we showed that spatially restricted Akt mediates between Sema4D-RhoA signaling and these downstream cellular events. Collectively, our results reveal a novel signaling network, the Sema4D-RhoA-Akt signal cascade, that coordinates cellular function and morphology and highlights the importance of specific spatiotemporally restricted components of a signaling pathway in the regulation of ameloblast differentiation. © 2016 American Society for Bone and Mineral Research.

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Sema4D, the Ligand for Plexin B1, Suppresses c-Met Activation and Migration and Promotes Melanocyte Survival and Growth

Cited by 45 publications

References 48 publications

Plexin B1 inhibits MET through direct association and regulates Shp2 expression in melanocytes

Plexin B1 inhibits MET through direct association and regulates Shp2 expression in melanocytes

Análise da atividade de CD100 na modulação da ativação de macrófagos e sua infectividade por Leishmania (Leishmania) amazonensis.

The Semaphorin 4D-RhoA-Akt Signal Cascade Regulates Enamel Matrix Secretion in Coordination With Cell Polarization During Ameloblast Differentiation

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