Dynamics, nanoscale organization, and function of synaptic adhesion molecules

Chamma, Ingrid; Thoumine, Olivier

doi:10.1016/j.mcn.2018.04.007

Cited by 19 publications

(16 citation statements)

References 180 publications

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“…Moreover, “early” and “late” synaptic genes are co-expressed and co-regulated in the same neuron, suggesting that their differential localization and combinatorial use define synapse specificity and network connectivity rules (Földy et al, 2016). Here, I will describe the major CAM families involved; for a complete list of CAMs in synapses, see recent reviews (Jang et al, 2017; Chamma and Thoumine, 2018).…”

Section: Cell Adhesion Molecules Initiate Specify and Regulate Synapsesmentioning

confidence: 99%

The Emerging Role of Mechanics in Synapse Formation and Plasticity

Kilinc

2018

Front. Cell. Neurosci.

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The regulation of synaptic strength forms the basis of learning and memory, and is a key factor in understanding neuropathological processes that lead to cognitive decline and dementia. While the mechanical aspects of neuronal development, particularly during axon growth and guidance, have been extensively studied, relatively little is known about the mechanical aspects of synapse formation and plasticity. It is established that a filamentous actin network with complex spatiotemporal behavior controls the dendritic spine shape and size, which is thought to be crucial for activity-dependent synapse plasticity. Accordingly, a number of actin binding proteins have been identified as regulators of synapse plasticity. On the other hand, a number of cell adhesion molecules (CAMs) are found in synapses, some of which form transsynaptic bonds to align the presynaptic active zone (PAZ) with the postsynaptic density (PSD). Considering that these CAMs are key components of cellular mechanotransduction, two critical questions emerge: (i) are synapses mechanically regulated? and (ii) does disrupting the transsynaptic force balance lead to (or exacerbate) synaptic failure? In this mini review article, I will highlight the mechanical aspects of synaptic structures—focusing mainly on cytoskeletal dynamics and CAMs—and discuss potential mechanoregulation of synapses and its relevance to neurodegenerative diseases.

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Section: Cell Adhesion Molecules Initiate Specify and Regulate Synapsesmentioning

confidence: 99%

The Emerging Role of Mechanics in Synapse Formation and Plasticity

Kilinc

2018

Front. Cell. Neurosci.

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“…NLGN3/4X have well established roles in synaptogenesis and spine formation, an effect mediated by the clustering of these proteins at synaptic sites which regulates actin cytoskeletal remodeling 26, 30, 32, 33 . We, therefore, reasoned that as WT NLGN3 and NLGN4X clustered at membranes of hNPCs and at the leading edge of growth cones in immature neurons, that these adhesion proteins may be involved in regulating membrane structures and neurite outgrowth.…”

Section: Resultsmentioning

confidence: 99%

“…One potential caveat of this approach could arise due to a compensatory mechanism induced by endogenous expression of NLGN3/4X. Indeed, previous studies have shown that up or down regulation of NLGNs can produce conflicting results, depending on the cellular context 32, 47, 48 . Alterations in the expression of NLGNs and their subsequent impact on their cellular function may, therefore, be obfuscated by other NLGNs.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, nanoscale clustering of the chemokine receptor CXCR4 at the leading edge of Jurkat T lymphocyte cells was found to promote dynamic actin rearrangement resulting in increased cell migration 52 . Evidence from mature neurons also suggests orchestrated nanoscale recruitment and clustering of cell-adhesion molecules (CAM) at synapses is critical to synaptic function 32 . For example, NLGN1 and N-cadherin were found to cooperate to form clusters at synapses in mature hippocampal neurons, ultimately promoting synapse formation 53 .…”

Section: Discussionmentioning

confidence: 99%

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Nanoscopic Clustering of Neuroligin-3 and Neuroligin-4X Regulates Growth Cone Organization and Size

Gatford¹,

Deans

Duarte³

et al. 2019

Preprint

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The cell-adhesion proteins neuroligin-3 and neuroligin-4X (NLGN3/4X) have well described roles in synapse formation. NLGN3/4X are also expressed highly during neurodevelopment. However, the role these proteins play during this period is unknown. Here we show that NLGN3/4X localized to the leading edge of growth cones where itpromoted neuritogenesis in immature human neurons. Super-resolution microscopyrevealed that NLGN3/4X clustering induced growth cone enlargement and influenced actin filament organization. Critically, these morphological effects were not induced by Autism spectrum condition (ASC)-associated NLGN3/4X variants. Finally, actin regulators p21-activated kinase 1 (PAK1) and cofilin were found to be activated by NLGN3/4X and involved in mediating the effects of these adhesion proteins on actin filaments, growth cones, and neuritogenesis. These data reveal a novel role for NLGN3 and NLGN4X in the development of neuronal architecture, which may be altered in the presence of ASD-associated variants.

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“…Studies have demonstrated that besides neuroligins, neurexins create trans-synaptic interactions also with several other proteins, particularly, neurexophilins, cerebellins, calsyntenins, as well as dystroglycans, and LRRTMs ( Südhof, 2017 ; Chamma and Thoumine, 2018 ). Briefly, neurexophilins comprise a family of four secreted glycoproteins (neurexophilin-1 to neurexophilin-4) ( Missler et al, 1998 ) that play an essential function in synaptic plasticity ( Born et al, 2014 ; Neupert et al, 2015 ).…”

Section: Pathophysiology Of Trans-synaptic Camsmentioning

confidence: 99%

Pathophysiology of Trans-Synaptic Adhesion Molecules: Implications for Epilepsy

Gorlewicz

Kaczmarek

2018

Front. Cell Dev. Biol.

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Chemical synapses are specialized interfaces between neurons in the brain that transmit and modulate information, thereby integrating cells into multiplicity of interacting neural circuits. Cell adhesion molecules (CAMs) might form trans-synaptic complexes that are crucial for the appropriate identification of synaptic partners and further for the establishment, properties, and dynamics of synapses. When affected, trans-synaptic adhesion mechanisms play a role in synaptopathies in a variety of neuropsychiatric disorders including epilepsy. This review recapitulates current understanding of trans-synaptic interactions in pathophysiology of interneuronal connections. In particular, we discuss here the possible implications of trans-synaptic adhesion dysfunction for epilepsy.

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Dynamics, nanoscale organization, and function of synaptic adhesion molecules

Cited by 19 publications

References 180 publications

The Emerging Role of Mechanics in Synapse Formation and Plasticity

The Emerging Role of Mechanics in Synapse Formation and Plasticity

Nanoscopic Clustering of Neuroligin-3 and Neuroligin-4X Regulates Growth Cone Organization and Size

Pathophysiology of Trans-Synaptic Adhesion Molecules: Implications for Epilepsy

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