BraInMap Elucidates the Macromolecular Connectivity Landscape of Mammalian Brain

Pourhaghighi, Mohammad Reza; Ash, Peter E.A.; Phanse, Sadhna; Goebels, Florian; Hu, Lucas; Chen, Siwei; Zhang, Yingying; Wierbowski, Shayne D.; Boudeau, Samantha; Moutaoufik, Mohamed Taha; Malty, Ramy H.; Małolepsza, Edyta; Tsafou, Kalliopi; Nathan, Aparna; Cromar, Graham; Guo, Hongbo; Abdullatif, Ali Al; Apicco, Daniel J.; Becker, Lindsay A.; Gitler, Aaron D.; Pulst, Stefan M.; Youssef, Ahmed; Hekman, Ryan; Havugimana, Pierre C.; White, Carl A.; Blum, Benjamin; Ratti, Antonia; Bryant, Camron D.; Parkinson, John; Lage, Kasper; Babu, Mohan; Yu, Haiyuan; Bader, Gary D.; Wolozin, Benjamin; Emili, Andrew

doi:10.1016/j.cels.2020.03.003

Cited by 63 publications

(58 citation statements)

References 111 publications

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“…Within this family, IgLON sub-family members include Negr1 (also known as Kilon), Lsamp, OPCML, and neurotrimin; these highly glycosylated proteins display three immunoglobulin domains and are anchored to the cell membrane by a glycosylphosphatidylinositol motif inserted in their C termini [16]. Lsamp direct interaction with Negr1 has been previously observed in protein microarray experiments [17] and recently confirmed in mouse brain [18]. Lsamp function in serotonergic signalling has been suggested by the findings that Lsamp -/mice showed lower 5-HT levels and higher 5-HT turnover, which have been called to explain their low anxiety and aggression [19,20].…”

Section: Introductionmentioning

confidence: 85%

Depression-Associated Gene Negr1-Fgfr2 Pathway Is Altered by Antidepressant Treatment

Carboni

Pischedda

Piccoli

et al. 2020

Cells

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The Negr1 gene has been significantly associated with major depression in genetic studies. Negr1 encodes for a cell adhesion molecule cleaved by the protease Adam10, thus activating Fgfr2 and promoting neuronal spine plasticity. We investigated whether antidepressants modulate the expression of genes belonging to Negr1-Fgfr2 pathway in Flinders sensitive line (FSL) rats, in a corticosterone-treated mouse model of depression, and in mouse primary neurons. Negr1 and Adam10 were the genes mostly affected by antidepressant treatment, and in opposite directions. Negr1 was down-regulated by escitalopram in the hypothalamus of FSL rats, by fluoxetine in the hippocampal dentate gyrus of corticosterone-treated mice, and by nortriptyline in hippocampal primary neurons. Adam10 mRNA was increased by nortriptyline administration in the hypothalamus, by escitalopram in the hippocampus of FSL rats, and by fluoxetine in mouse dorsal dentate gyrus. Similarly, nortriptyline increased Adam10 expression in hippocampal cultures. Fgfr2 expression was increased by nortriptyline in the hypothalamus of FSL rats and in hippocampal neurons. Lsamp, another IgLON family protein, increased in mouse dentate gyrus after fluoxetine treatment. These findings suggest that Negr1-Fgfr2 pathway plays a role in the modulation of synaptic plasticity induced by antidepressant treatment to promote therapeutic efficacy by rearranging connectivity in corticolimbic circuits impaired in depression.

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Section: Introductionmentioning

confidence: 85%

Depression-Associated Gene Negr1-Fgfr2 Pathway Is Altered by Antidepressant Treatment

Carboni

Pischedda

Piccoli

et al. 2020

Cells

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“…Recent proteomic studies identified proteins associated with M6a that participate in neurite outgrowth and axon elongation ( Figures 1B,C ; Sato et al, 2011a ; Huttlin et al, 2017 ; Aparicio et al, 2020 ; Haenig et al, 2020 ; Pourhaghighi et al, 2020 ). To emphasize some examples, we divided them into 3 groups: (i) Cytoplasmic proteins: which include cytoskeleton adaptor molecules and cytoskeleton organization pathways which might interact with M6a’s cytoplasmic tails as Ras kinases 2, DiRas2 ( Grunewald et al, 2021 ) and the kinases mentioned above.…”

Section: M6a and Synapse Formationmentioning

confidence: 99%

“…This subject exceeds the topics covered in this review, and no functional experiments were reported yet, but we would like to highlight a few insights. Pourhaghighi et al (2020) identified associated protein complexes in adult mammal brains and built BraInMap 2 . M6a was found within a complex of 30 interacting proteins, some of which are myelin sheath proteins, including the main myelin glycoproteins PLP and MAG; or are myelin sheath associated proteins like contactin 1 and contactin associated protein 1.…”

Section: M6a’s Potential Role In Neuron-glia Interactionmentioning

confidence: 99%

Neuronal Glycoprotein M6a: An Emerging Molecule in Chemical Synapse Formation and Dysfunction

León

Aparicio

Scorticati

2021

Front. Synaptic Neurosci.

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The cellular and molecular mechanisms underlying neuropsychiatric and neurodevelopmental disorders show that most of them can be categorized as synaptopathies—or damage of synaptic function and plasticity. Synaptic formation and maintenance are orchestrated by protein complexes that are in turn regulated in space and time during neuronal development allowing synaptic plasticity. However, the exact mechanisms by which these processes are managed remain unknown. Large-scale genomic and proteomic projects led to the discovery of new molecules and their associated variants as disease risk factors. Neuronal glycoprotein M6a, encoded by the GPM6A gene is emerging as one of these molecules. M6a has been involved in neuron development and synapse formation and plasticity, and was also recently proposed as a gene-target in various neuropsychiatric disorders where it could also be used as a biomarker. In this review, we provide an overview of the structure and molecular mechanisms by which glycoprotein M6a participates in synapse formation and maintenance. We also review evidence collected from patients carrying mutations in the GPM6A gene; animal models, and in vitro studies that together emphasize the relevance of M6a, particularly in synapses and in neurological conditions.

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“…The laboratory mouse, Mus musculus, is possibly the most important model species that has been used extensively in the study of genetics [299]. Due to its importance to the understanding of human disease, the mouse interactome has been a key research goal since completion of the mouse genome, and a wealth of experimental [89,[300][301][302][303][304][305][306][307][308] and computational [13,64,188,198,[309][310][311][312] interactome data have been produced, which along with human and yeast data, form the basis of interactome studies in many other mammals (Table 6). One of the largest, MouseNet, represents a large-scale PFIN produced via machine learning based on multiple types of functional interaction data including PPIs, expression and phenotypes.…”

Section: Mammalsmentioning

confidence: 99%

Expanding Interactome Analyses beyond Model Eukaryotes

James¹,

Wipat²,

Cockell³

2021

Preprint

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Interactome analyses have traditionally been applied to yeast, human and other model organisms due to the availability of protein-protein interactions data for these species. Recently these techniques have been applied to more diverse species using computational interaction prediction from genome sequence and other data types. This review describes the various types of computational interactome networks that can be created and how they have been used in diverse eukaryotic species, highlighting some of the key interactome studies in non-model organisms.

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BraInMap Elucidates the Macromolecular Connectivity Landscape of Mammalian Brain

Cited by 63 publications

References 111 publications

Depression-Associated Gene Negr1-Fgfr2 Pathway Is Altered by Antidepressant Treatment

Depression-Associated Gene Negr1-Fgfr2 Pathway Is Altered by Antidepressant Treatment

Neuronal Glycoprotein M6a: An Emerging Molecule in Chemical Synapse Formation and Dysfunction

Expanding Interactome Analyses beyond Model Eukaryotes

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