Immunomodulatory Functions of Neuronal Guidance Proteins

Mirakaj, Valbona; Rosenberger, Peter

doi:10.1016/j.it.2017.03.007

Cited by 50 publications

(50 citation statements)

References 87 publications

(78 reference statements)

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“…Neuropilins (Nrps) are coreceptors for secreted Semaphorin ligands and cobind with Plexin receptors. Nrps have been implicated in neurogenesis and angiogenesis (36,37); however, no role has so far been found in adiposity. We recently identified that Plexin D1 (plxnd1) mutant zebrafish have altered regional adiposity, characterized by reduced levels of VAT (38,39).…”

Section: Discussionmentioning

confidence: 99%

Deep phenotyping in zebrafish reveals genetic and diet-induced adiposity changes that may inform disease risk

Minchin

Scahill

Staudt

et al. 2018

Journal of Lipid Research

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The regional distribution of adipose tissues is implicated in a wide range of diseases. For example, proportional increases in visceral adipose tissue increase the risk for insulin resistance, diabetes, and CVD. Zebrafish offer a tractable model system by which to obtain unbiased and quantitative phenotypic information on regional adiposity, and deep phenotyping can explore complex disease-related adiposity traits. To facilitate deep phenotyping of zebrafish adiposity traits, we used pairwise correlations between 67 adiposity traits to generate stage-specific adiposity profiles that describe changing adiposity patterns and relationships during growth. Linear discriminant analysis classified individual fish according to an adiposity profile with 87.5% accuracy. Deep phenotyping of eight previously uncharacterized zebrafish mutants identified as a novel gene that alters adipose distribution. When we applied deep phenotyping to identify changes in adiposity during diet manipulations, zebrafish that underwent food restriction and refeeding had widespread adiposity changes when compared with continuously fed, equivalently sized control animals. In particular, internal adipose tissues (e.g., visceral adipose) exhibited a reduced capacity to replenish lipid following food restriction. Together, these results in zebrafish establish a new deep phenotyping technique as an unbiased and quantitative method to help uncover new relationships between genotype, diet, and adiposity.

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Section: Discussionmentioning

confidence: 99%

Deep phenotyping in zebrafish reveals genetic and diet-induced adiposity changes that may inform disease risk

Minchin

Scahill

Staudt

et al. 2018

Journal of Lipid Research

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“…Neogenin was first identified as an axon guidance receptor for both Netrin-1 and the repulsive guidance molecules and also regulates neural migration in the adult and embryonic brain (O'Leary et al, 2015;Rajagopalan et al, 2004;Siebold et al, 2017;van Erp et al, 2015). In addition, it plays a central role in the mobilization of inflammatory cells in response to injury and infection (Mirakaj and Rosenberger, 2017). During migration, attractive or repulsive responses to guidance cues are dictated by remodeling of the actin cytoskeleton, which promotes the extension and retraction of lamellipodia upon receptor activation.…”

Section: Discussionmentioning

confidence: 99%

Neogenin Recruitment of the WAVE Regulatory Complex to Ependymal and Radial Progenitor Adherens Junctions Prevents Hydrocephalus

et al. 2017

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Denudation of the ependyma due to loss of cell adhesion mediated by cadherin-based adherens junctions is a common feature of perinatal hydrocephalus. Junctional stability depends on the interaction between cadherins and the actin cytoskeleton. However, the molecular mechanism responsible for recruiting the actin nucleation machinery to the ependymal junction is unknown. Here, we reveal that loss of the netrin/RGM receptor, Neogenin, leads to severe hydrocephalus. We show that Neogenin plays a critical role in actin nucleation in the ependyma by anchoring the WAVE regulatory complex (WRC) and Arp2/3 to the cadherin complex. Blocking Neogenin binding to the Cyfip1/Abi WRC subunit results in actin depolymerization, junctional collapse, and denudation of the postnatal ventricular zone. In the embryonic cortex, this leads to loss of radial progenitor adhesion, aberrant neuronal migration, and neuronal heterotopias. Therefore, Neogenin-WRC interactions play a fundamental role in ensuring the fidelity of the embryonic ventricular zone and maturing ependyma.

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“…In addition, the vagus nerve controls the expression of the neuronal guidance protein (NGP) Netrin-1, 40 which regulates not only neuronal development but also inflammatory responses. [42][43][44][45] After vagotomy and peritonitis, the expression of Netrin-1 was substantially decreased, indicating an involvement of Netrin-1 in this neuroimmune interaction. 40 During peritonitis, Netrin-1 shortens the time required for resolution and promotes the synthesis of endogenous proresolving mediators.…”

Section: Vagus Nerve During Resolution Of Sterile and Infectious Perimentioning

confidence: 99%

“…47 The protein RGM-A was shown to substantially influence the initial phase of acute inflammation and the pathobiology of autoimmune encephalomyelitis. 43,48,49 In a study by Körner and colleagues, 47 Notes: The adrenergic nerve together with the neuronal guidance protein RGM-A activate resolution programmes. RGM-A enhances the expression of the β2 adrenergic receptor (β2AR) on human MΦs, and activation of β2AR, in turn, increases RGM-A expression on MΦs.…”

Section: Sympathetic Nerve In Resolution and Tissue Regenerationmentioning

confidence: 99%

<p>Novel Resolution Mediators of Severe Systemic Inflammation</p>

Gudernatsch¹,

Stefanczyk²,

Mirakaj³

2020

ITT

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Nonresolving inflammation, a hallmark of underlying severe inflammatory processes such as sepsis, acute respiratory distress syndrome and multiple organ failure is a major cause of admission to the intensive care unit and high mortality rates. Many survivors develop new functional limitations and health problems, and in cases of sepsis, approximately 40% of patients are rehospitalized within three months. Over the last few decades, better treatment approaches have been adopted. Nevertheless, the lack of knowledge underlying the complex pathophysiology of the inflammatory response organized by numerous mediators and the induction of complex networks impede curative therapy. Thus, increasing evidence indicates that resolution of an acute inflammatory response, considered an active process, is the ideal outcome that leads to tissue restoration and organ function. Many mediators have been identified as immunoresolvents, but only a few have been shown to contribute to both the initial and resolution phases of severe systemic inflammation, and these agents might finally substantially impact the therapeutic approach to severe inflammatory processes. In this review, we depict different resolution mediators/immunoresolvents contributing to resolution programmes specifically related to life-threatening severe inflammatory processes.

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Immunomodulatory Functions of Neuronal Guidance Proteins

Cited by 50 publications

References 87 publications

Deep phenotyping in zebrafish reveals genetic and diet-induced adiposity changes that may inform disease risk

Deep phenotyping in zebrafish reveals genetic and diet-induced adiposity changes that may inform disease risk

Neogenin Recruitment of the WAVE Regulatory Complex to Ependymal and Radial Progenitor Adherens Junctions Prevents Hydrocephalus

<p>Novel Resolution Mediators of Severe Systemic Inflammation</p>

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