Molecular Mechanisms of L1 and NCAM Adhesion Molecules in Synaptic Pruning, Plasticity, and Stabilization

Duncan, Bryce W.; Murphy, Kelsey E.; Maness, Patricia F.

doi:10.3389/fcell.2021.625340

Cited by 45 publications

(44 citation statements)

References 150 publications

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“…The human homolog NCAM1 encodes a cell adhesion protein of the immunoglobulin superfamily that regulates cell-cell and cell-matrix interactions during development and differentiation processes (Duncan et al, 2021; Siles et al, 2018). The Zebrafish Regeneration Database recorded that ncam1a RNA levels increase during heart, fin, or spinal cord regeneration (Figure S4).…”

Section: Resultsmentioning

confidence: 99%

Identification of enhancer regulatory elements that direct epicardial gene expression during zebrafish heart regeneration

Cao

Xia

Balowski

et al. 2021

Preprint

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The epicardium is a mesothelial tissue layer that envelops the heart. Cardiac injury activates dynamic gene expression programs in epicardial tissue, which in the case of zebrafish enables subsequent regeneration through paracrine and vascularizing effects. To identify tissue regeneration enhancer elements (TREEs) that control injury-induced epicardial gene expression during heart regeneration, we profiled transcriptomes and chromatin accessibility in epicardial cells purified from regenerating zebrafish hearts. We identified hundreds of candidate TREEs, defined by increased chromatin accessibility of non-coding elements near genes with increased expression during regeneration. Several of these candidate TREEs were incorporated into stable transgenic lines, with 5 of 6 elements directing injury-induced epicardial expression but not ontogenetic epicardial expression in hearts of larval animals. Whereas two independent TREEs linked to the gene gnai3 showed similar functional features of gene regulation in transgenic lines, two independent ncam1a-linked TREEs directed distinct spatiotemporal domains of epicardial gene expression. Thus, multiple TREEs linked to a regeneration gene can possess either matching or complementary regulatory controls. Our study provides a new resource and principles for understanding the regulation of epicardial genetic programs during heart regeneration.

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Section: Resultsmentioning

confidence: 99%

Identification of enhancer regulatory elements that direct epicardial gene expression during zebrafish heart regeneration

Cao

Xia

Balowski

et al. 2021

Preprint

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“…Neurofascin) play diverse and essential roles in the developing brain by promoting axon growth, cell adhesion, and migration [4]. L1-CAMs also mediate repellent axon guidance in response to class 3 Semaphorins [5][6][7], which are secreted ligands that stimulate growth cone collapse and axon repulsion [8].…”

Section: L1 Family Cell Adhesion Molecules (L1 Nrcam Close Homologymentioning

confidence: 99%

Semaphorin3F Drives Dendritic Spine Pruning through Rho-GTPase Signaling

Duncan

Mohan

Wade

et al. 2021

Preprint

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Dendritic spines of cortical pyramidal neurons are initially overproduced then remodeled substantially in the adolescent brain to achieve appropriate excitatory balance in mature circuits. Here we investigated the molecular mechanism of developmental spine pruning by Semaphorin 3F (Sema3F) and its holoreceptor complex, which consists of immunoglobulin-class adhesion molecule NrCAM, Neuropilin-2 (Npn2), and PlexinA3 (PlexA3) signaling subunits. Structure-function studies of the NrCAM-Npn2 interface showed that NrCAM stabilizes binding between Npn2 and PlexA3 necessary for Sema3F-induced spine pruning. Using a mouse neuronal culture system, we identified a dual signaling pathway for Sema3F-induced pruning, which involves activation of Tiam1-Rac1-PAK1-3 -LIMK1/2-Cofilin1 and RhoA-ROCK1/2-Myosin II in dendritic spines. Inhibitors of actin remodeling impaired spine collapse in the cortical neurons. Elucidation of these pathways expands our understanding of critical events that sculpt neuronal networks and may provide insight into how interruptions to these pathways could lead to spine dysgenesis in diseases such as autism, bipolar disorder, and schizophrenia.

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“…The CAM family plays critical roles in synaptic pruning, plasticity, stabilization ( Duncan et al, 2021 ), tumor-associated pathways ( Duraivelan and Samanta, 2021 ), etc. Loss of 4.1B in the axon is associated with reduced levels of CAM1 and CAM3 ( Einheber et al, 2013 ).…”

Section: 1n In the Nerve Systemmentioning

confidence: 99%

4.1N-Mediated Interactions and Functions in Nerve System and Cancer

Yang

Liu

Wang

2021

Front. Mol. Biosci.

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Scaffolding protein 4.1N is a neuron-enriched 4.1 homologue. 4.1N contains three conserved domains, including the N-terminal 4.1-ezrin-radixin-moesin (FERM) domain, internal spectrin–actin–binding (SAB) domain, and C-terminal domain (CTD). Interspersed between the three domains are nonconserved domains, including U1, U2, and U3. The role of 4.1N was first reported in the nerve system. Then, extensive studies reported the role of 4.1N in cancers and other diseases. 4.1N performs numerous vital functions in signaling transduction by interacting, locating, supporting, and coordinating different partners and is involved in the molecular pathogenesis of various diseases. In this review, recent studies on the interactions between 4.1N and its contactors (including the α7AChr, IP3R1, GluR1/4, GluK1/2/3, mGluR8, KCC2, D2/3Rs, CASK, NuMA, PIKE, IP6K2, CAM 1/3, βII spectrin, flotillin-1, pp1, and 14-3-3) and the 4.1N-related biological functions in the nerve system and cancers are specifically and comprehensively discussed. This review provides critical detailed mechanistic insights into the role of 4.1N in disease relationships.

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Molecular Mechanisms of L1 and NCAM Adhesion Molecules in Synaptic Pruning, Plasticity, and Stabilization

Cited by 45 publications

References 150 publications

Identification of enhancer regulatory elements that direct epicardial gene expression during zebrafish heart regeneration

Identification of enhancer regulatory elements that direct epicardial gene expression during zebrafish heart regeneration

Semaphorin3F Drives Dendritic Spine Pruning through Rho-GTPase Signaling

4.1N-Mediated Interactions and Functions in Nerve System and Cancer

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