The SynCAM synaptic cell adhesion molecules are involved in sensory axon pathfinding by regulating axon-axon contacts

Frei, Jeannine A.; Andermatt, Irwin; Gesemann, Matthias; Stoeckli, Esther T.

doi:10.1242/dev.120535

Cited by 10 publications

(24 citation statements)

References 19 publications

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“…Initially, it was reported that SynCAMs would preferentially form cis-homodimers which would interact homo-and heterophilically with dimers in trans (Takai et al, 2008;Fogel et al, 2007). It is clear now that the interaction pattern is even more complex and cis-heterodimers are clearly formed Fogel et al, 2011;Frei et al, 2014). Furthermore, the composition of cis-dimers determines the affinities for trans-interactions, similar to what was found previously for other IgSF CAMs Kunz et al, 2002).…”

Section: Syncams Go the Other Way: Inducers Of Synapsessupporting

confidence: 71%

“…The existence of such heterophilic cis-interactions was confirmed by in vitro binding studies (Frei et al, 2014). Furthermore, these studies indicated that the nature of the cis-interaction determined the binding partners in trans, as heterophilic cis-interactions changed the binding preferences of trans-binding SynCAMs compared to cishomodimers (Frei et al, 2014). …”

Section: Syncams As Axon Guidance Molecules In the Cnsmentioning

confidence: 89%

“…The most likely explanation why axons required both SynCAM1 and SynCAM2 for their interaction with the floor plate was a heterophilic cis-interaction between SynCAM1 and SynCAM2 (Niederkofler et al, 2010). The existence of such heterophilic cis-interactions was confirmed by in vitro binding studies (Frei et al, 2014). Furthermore, these studies indicated that the nature of the cis-interaction determined the binding partners in trans, as heterophilic cis-interactions changed the binding preferences of trans-binding SynCAMs compared to cishomodimers (Frei et al, 2014).…”

Section: Syncams As Axon Guidance Molecules In the Cnsmentioning

confidence: 95%

“…As axonal receptors for floor-plate SynCAM2 both SynCAM1 and SynCAM2 itself were possible. However, SynCAM2-SynCAM2 interactions were found to be extremely weak in comparison to heterophilic SynCAM1-SynCAM2 interactions (Frei et al, 2014;Niederkofler et al, 2010;Fogel et al, 2007). Therefore, it came as a surprise when loss of SynCAM2 function from dI1 neurons also resulted in axon guidance defects at the midline.…”

Section: Syncams As Axon Guidance Molecules In the Cnsmentioning

confidence: 99%

“…Because of the subpopulation-specific expression of SynCAMs in sensory neurons of the dorsal root ganglia, they were tested for a role in axon guidance in the peripheral nervous system (Frei et al, 2014).…”

Section: Syncams As Axon Guidance Molecules In the Pnsmentioning

confidence: 99%

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SynCAMs – From axon guidance to neurodevelopmental disorders

Frei

Stoeckli

2017

Molecular and Cellular Neuroscience

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Many cell adhesion molecules are located at synapses but only few of them can be considered synaptic cell adhesion molecules in the strict sense. Besides the Neurexins and Neuroligins, the LRRTMs (leucine rich repeat transmembrane proteins) and the SynCAMs/CADMs can induce synapse formation when expressed in non-neuronal cells and therefore are true synaptic cell adhesion molecules. SynCAMs (synaptic cell adhesion molecules) are a subfamily of the immunoglobulin superfamily of cell adhesion molecules. As suggested by their name, they were first identified as cell adhesion molecules at the synapse which were sufficient to trigger synapse formation. They also contribute to myelination by mediating axon-glia cell contacts. More recently, their role in earlier stages of neural circuit formation was demonstrated, as they also guide axons both in the peripheral and in the central nervous system. Mutations in SynCAM genes were found in patients diagnosed with autism spectrum disorders. The diverse functions of SynCAMs during development suggest that neurodevelopmental disorders are not only due to defects in synaptic plasticity. Rather, early steps of neural circuit formation are likely to contribute. Many cell adhesion molecules are located at synapses but only few of them can be considered synaptic cell adhesion molecules in the strict sense. Besides the Neurexins and Neuroligins, the LRRTMs (leucine rich repeat transmembrane proteins) and the SynCAMs/CADMs can induce synapse formation when expressed in non-neuronal cells and therefore are true synaptic cell adhesion molecules. SynCAMs (synaptic cell adhesion molecules) are a subfamily of the immunoglobulin superfamily of cell adhesion molecules. As suggested by their name, they were first identified as cell adhesion molecules at the synapse which were sufficient to trigger synapse formation. They also contribute to myelination by mediating axon-glia cell contacts. More recently, their role in earlier stages of neural circuit formation was demonstrated, as they also guide axons both in the peripheral and in the central nervous system. Mutations in SynCAM genes were found in patients diagnosed with autism spectrum disorders. The diverse functions of SynCAMs during development suggest that neurodevelopmental disorders are not only due to defects in synaptic plasticity. Rather, early steps of neural circuit formation are likely to contribute.

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Section: Syncams Go the Other Way: Inducers Of Synapsessupporting

confidence: 71%

Section: Syncams As Axon Guidance Molecules In the Cnsmentioning

confidence: 89%

Section: Syncams As Axon Guidance Molecules In the Cnsmentioning

confidence: 95%

Section: Syncams As Axon Guidance Molecules In the Cnsmentioning

confidence: 99%

Section: Syncams As Axon Guidance Molecules In the Pnsmentioning

confidence: 99%

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SynCAMs – From axon guidance to neurodevelopmental disorders

Frei

Stoeckli

2017

Molecular and Cellular Neuroscience

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Diversity of satellite glia in sympathetic and sensory ganglia

et al. 2022

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Satellite glia are the major glial type found in sympathetic and sensory ganglia in the peripheral nervous system, and specifically, contact neuronal cell bodies. Sympathetic and sensory neurons differ in morphological, molecular, and electrophysiological properties. However, the molecular diversity of the associated satellite glial cells remains unclear. Here, using single-cell RNA sequencing analysis, we identify five different populations of satellite glia from sympathetic and sensory ganglia. We define three shared populations of satellite glia enriched in immune-response genes, immediate-early genes, and ion channels/ECM-interactors, respectively. Sensory-and sympathetic-specific satellite glia are differentially enriched for modulators of lipid synthesis and metabolism. Sensory glia are also specifically enriched for genes involved in glutamate turnover. Furthermore, satellite glia and Schwann cells can be distinguished by unique transcriptional signatures. This study reveals the remarkable heterogeneity of satellite glia in the peripheral nervous system.

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The neurobiology of irritable bowel syndrome

Mayer¹,

Ryu

Bhatt

2023

Mol Psychiatry

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Irritable bowel syndrome (IBS) is the most prevalent disorder of brain-gut interactions that affects between 5 and 10% of the general population worldwide. The current symptom criteria restrict the diagnosis to recurrent abdominal pain associated with altered bowel habits, but the majority of patients also report non-painful abdominal discomfort, associated psychiatric conditions (anxiety and depression), as well as other visceral and somatic pain-related symptoms. For decades, IBS was considered an intestinal motility disorder, and more recently a gut disorder. However, based on an extensive body of reported information about central, peripheral mechanisms and genetic factors involved in the pathophysiology of IBS symptoms, a comprehensive disease model of brain-gut-microbiome interactions has emerged, which can explain altered bowel habits, chronic abdominal pain, and psychiatric comorbidities. In this review, we will first describe novel insights into several key components of brain-gut microbiome interactions, starting with reported alterations in the gut connectome and enteric nervous system, and a list of distinct functional and structural brain signatures, and comparing them to the proposed brain alterations in anxiety disorders. We will then point out the emerging correlations between the brain networks with the genomic, gastrointestinal, immune, and gut microbiome-related parameters. We will incorporate this new information into a systems-based disease model of IBS. Finally, we will discuss the implications of such a model for the improved understanding of the disorder and the development of more effective treatment approaches in the future.

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The SynCAM synaptic cell adhesion molecules are involved in sensory axon pathfinding by regulating axon-axon contacts

Cited by 10 publications

References 19 publications

SynCAMs – From axon guidance to neurodevelopmental disorders

SynCAMs – From axon guidance to neurodevelopmental disorders

Diversity of satellite glia in sympathetic and sensory ganglia

The neurobiology of irritable bowel syndrome

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