ICAM-5: A Neuronal Dendritic Adhesion Molecule Involved in Immune and Neuronal Functions

Gahmberg, Carl G.; Lin, Ning; Paetau, Sonja

doi:10.1007/978-1-4614-8090-7_6

Cited by 24 publications

(21 citation statements)

References 65 publications

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“…6G). These data correlate with the known expression of ICAM-5 as a somatodendritic, but not axonal, adhesion molecule (30,33). Due to a lack of expression on the axon, ICAM-5 is unlikely to play a role in axonal infection and retrograde transport for sialic acid-independent EV-D68 strains, as only axons cross the microgrooves, as previously shown in Fig.…”

supporting

confidence: 88%

“…So far, intracellular adhesion molecule 5 (ICAM-5)/telencephalin is the only CNS protein receptor candidate that has been identified for EV-D68 (21). In vivo ICAM-5 expression is strictly localized to the neuronal dendrites and cell bodies within the cerebral cortex and olfactory bulbs or telencephalon (30)(31)(32)(33). To confirm this pattern of in vivo expression, we obtained human brain and spinal cord samples for Western blot analysis.…”

mentioning

confidence: 95%

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Contemporary Circulating Enterovirus D68 Strains Infect and Undergo Retrograde Axonal Transport in Spinal Motor Neurons Independent of Sialic Acid

Hixon

Clarke²,

Tyler

2019

J Virol

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Enterovirus D68 (EV-D68) is an emerging virus that has been identified as a cause of recent outbreaks of acute flaccid myelitis (AFM), a poliomyelitis-like spinal cord syndrome that can result in permanent paralysis and disability. In experimental mouse models, EV-D68 spreads to, infects, and kills spinal motor neurons following infection by various routes of inoculation. The topography of virus-induced motor neuron loss correlates with the pattern of paralysis. The mechanism(s) by which EV-D68 spreads to target motor neurons remains unclear. We sought to determine the capacity of EV-D68 to spread by the neuronal route and to determine the role of known EV-D68 receptors, sialic acid and intracellular adhesion molecule 5 (ICAM-5), in neuronal infection. To do this, we utilized a microfluidic chamber culture system in which human induced pluripotent stem cell (iPSC) motor neuron cell bodies and axons can be compartmentalized for independent experimental manipulation. We found that EV-D68 can infect motor neurons via their distal axons and spread by retrograde axonal transport to the neuronal cell bodies. Virus was not released from the axons via anterograde axonal transport after infection of the cell bodies. Prototypic strains of EV-D68 depended on sialic acid for axonal infection and transport, while contemporary circulating strains isolated during the 2014 EV-D68 outbreak did not. The pattern of infection did not correspond with the ICAM-5 distribution and expression in either human tissue, the mouse model, or the iPSC motor neurons. IMPORTANCE Enterovirus D68 (EV-D68) infections are on the rise worldwide. Since 2014, the United States has experienced biennial spikes in EV-D68-associated acute flaccid myelitis (AFM) that have left hundreds of children paralyzed. Much remains to be learned about the pathogenesis of EV-D68 in the central nervous system (CNS). Herein we investigated the mechanisms of EV-D68 CNS invasion through neuronal pathways. A better understanding of EV-D68 infection in experimental models may allow for better prevention and treatment strategies of EV-D68 CNS disease.

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supporting

confidence: 88%

mentioning

confidence: 95%

Contemporary Circulating Enterovirus D68 Strains Infect and Undergo Retrograde Axonal Transport in Spinal Motor Neurons Independent of Sialic Acid

Hixon

Clarke²,

Tyler

2019

J Virol

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“…In hippocampal CA3-CA1 and cortical synapses, MMP-9 cleaves the membrane adhesion protein ICAM-5 that is most abundant on dendritic filopodia (Tian et al, 2007 ; Lonskaya et al, 2013 ). In neuronal cultures postsynaptic ICAM-5 interacts with presynaptic β1 integrin and blocks structural transition from filopodium to mature spine (Ning et al, 2013 ; Gahmberg et al, 2014 ). ICAM-5 cleavage promotes spine maturation and release of soluble extracellular domain of ICAM-5 increases synaptic AMPA receptor expression and cofilin phosphorylation (Lonskaya et al, 2013 ).…”

Section: The Role Of Extracellular Proteolysis In Structural and Funcmentioning

confidence: 99%

Extracellular proteolysis in structural and functional plasticity of mossy fiber synapses in hippocampus

Wiera

Mozrzymas

2015

Front. Cell. Neurosci.

108

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Brain is continuously altered in response to experience and environmental changes. One of the underlying mechanisms is synaptic plasticity, which is manifested by modification of synapse structure and function. It is becoming clear that regulated extracellular proteolysis plays a pivotal role in the structural and functional remodeling of synapses during brain development, learning and memory formation. Clearly, plasticity mechanisms may substantially differ between projections. Mossy fiber synapses onto CA3 pyramidal cells display several unique functional features, including pronounced short-term facilitation, a presynaptically expressed long-term potentiation (LTP) that is independent of NMDAR activation, and NMDA-dependent metaplasticity. Moreover, structural plasticity at mossy fiber synapses ranges from the reorganization of projection topology after hippocampus-dependent learning, through intrinsically different dynamic properties of synaptic boutons to pre- and postsynaptic structural changes accompanying LTP induction. Although concomitant functional and structural plasticity in this pathway strongly suggests a role of extracellular proteolysis, its impact only starts to be investigated in this projection. In the present report, we review the role of extracellular proteolysis in various aspects of synaptic plasticity in hippocampal mossy fiber synapses. A growing body of evidence demonstrates that among perisynaptic proteases, tissue plasminogen activator (tPA)/plasmin system, β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) and metalloproteinases play a crucial role in shaping plastic changes in this projection. We discuss recent advances and emerging hypotheses on the roles of proteases in mechanisms underlying mossy fiber target specific synaptic plasticity and memory formation.

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“…Finally, AK082527 lncRNA is expressed in an anti-sense direction relative to the Icam5 gene, which is very suggestive of a cis-regulatory role for this lncRNA in Icam5 expression. Icam5 is a neural-specific cell adhesion protein which appears to be key to dendritic extension and functional synapse formation 91 . At this time, there has been no report of its regulation by lncRNA.…”

Section: New Studiesmentioning

confidence: 99%

A molecular conundrum involving hypothalamic responses to and roles of long non-coding RNAs following food deprivation

Jiang

Good

2016

Molecular and Cellular Endocrinology

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Long non-coding RNAs (lncRNAs) are one of most poorly understood RNA classes in the mammalian transcriptome. However, they are emerging as important players in transcriptional regulation, especially within the complexity of the nervous system. This review summarizes the known information about lncRNAs, and their roles in endocrine processes, as well as the lesser-known information about lncRNAs in the brain, and in the neuroendocrine hypothalamus. A “call-to-action” is presented for researchers to use archival transcriptome data to characterize differentially expressed lncRNA species within the hypothalamus. In accordance, we analyze for differential-expression of lncRNA between normal mice and mice with a targeted deletion of the nescient helix-loop-helix 2 gene, and between C57Bl/6 and 129Sv/J mice. Finally, strategies and approaches for researchers to analyze their own datasets or those on the NCBI GEO datasets repository are provided, in hopes that future studies will reveal many new roles for lncRNAs in hypothalamic physiological responses, solving this so-called “molecular conundrum” once and for all.

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ICAM-5: A Neuronal Dendritic Adhesion Molecule Involved in Immune and Neuronal Functions

Cited by 24 publications

References 65 publications

Contemporary Circulating Enterovirus D68 Strains Infect and Undergo Retrograde Axonal Transport in Spinal Motor Neurons Independent of Sialic Acid

Contemporary Circulating Enterovirus D68 Strains Infect and Undergo Retrograde Axonal Transport in Spinal Motor Neurons Independent of Sialic Acid

Extracellular proteolysis in structural and functional plasticity of mossy fiber synapses in hippocampus

A molecular conundrum involving hypothalamic responses to and roles of long non-coding RNAs following food deprivation

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