Axonal Spectrins: Nanoscale Organization, Functional Domains and Spectrinopathies

Liu, Cheng-Hsin; Rasband, Matthew N.

doi:10.3389/fncel.2019.00234

Cited by 28 publications

(15 citation statements)

References 95 publications

(154 reference statements)

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“…New perturbation strategies with better molecular, spatial and temporal specificity such as optically-driven inhibitors will allow to dissect the role of the MPS in axonal physiological processes, before zooming out to assess the consequences on neuronal connectivity and information processing. Finally, potential dysfunctions of the MPS in neuropsychiatric diseases, from spectrinopathies [68,69] to Alzheimer's disease, remain to be explored.…”

Section: Discussionmentioning

confidence: 99%

Putting the axonal periodic scaffold in order

Leterrier

2021

Current Opinion in Neurobiology

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Neurons rely on a unique organization of their cytoskeleton to build, maintain and transform their extraordinarily intricate shapes. After decades of research on the neuronal cytoskeleton, it is exciting that novel assemblies are still discovered thanks to progress in cellular imaging methods. Indeed, super-resolution microscopy has revealed that axons are lined with a periodic scaffold of actin rings, spaced every 190 nm by spectrins. Determining the architecture, composition, dynamics, and functions of this membraneassociated periodic scaffold is a current conceptual and technical challenge, as well as a very active area of research. This short review aims at summarizing the latest research on the axonal periodic scaffold, highlighting recent progress and open questions.

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Section: Discussionmentioning

confidence: 99%

Putting the axonal periodic scaffold in order

Leterrier

2021

Current Opinion in Neurobiology

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“…It was also observed that cortical spectrin is more prominent towards the apical surface of MBE-F cells (Figure 1). These observations are perhaps not surprising considering spectrin is a multifunctional protein that is important not only for providing strength and stability to the plasma membrane [51,52] and organisation of cytoskeleton [44], but also plays an important role in cell polarity [53], regulation of ion channels [54], and assembly of excitable axon domains [55]. It is well established that the spectrin meshwork under the plasma membrane of erythrocytes hinders the release of plasma membrane EVs [24].…”

Section: Discussionmentioning

confidence: 99%

Membrane to cytosol redistribution of αII‐spectrin drives extracellular vesicle biogenesis in malignant breast cells

et al. 2021

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Spectrin is a ubiquitous cytoskeletal protein that provides structural stability and supports membrane integrity. In erythrocytes, spectrin proteolysis leads to the biogenesis of plasma membrane extracellular vesicles (EVs). However, its role in non-erythroid or cancer-derived plasma membrane EVs biogenesis is unknown. This study aims to examine the role of αII-spectrin in malignant and non-malignant plasma membrane vesiculation. We developed a custom, automated cell segmentation plugin for the image processor, Fiji, that provides an unbiased assessment of high resolution confocal microscopy images of the subcellular distribution of αII-spectrin. We show that, in low vesiculating non-malignant MBE-F breast cells, prominent cortical spectrin localises to the cell periphery at rest. In comparison, cortical spectrin is diminished in high vesiculating malignant MCF-7 breast cells at rest. A cortical distribution of spectrin correlates with increased biomechanical stiffness as measured by Atomic Force Microscopy. Furthermore, cortical spectrin can be induced in malignant MCF-7 cells by treatment with known vesiculation modulators including the calcium chelator, BAPTA-AM or the calpain inhibitor II (ALLM). These results demonstrate that the subcellular localisation of spectrin is distinctly different in malignant and non-malignant cells at rest and shows that the redistribution of cortical αII-spectrin to the cytoplasm supports plasma membrane-derived EV biogenesis in malignant cells. K E Y W O R D S calcium, cancer, cytoskeleton, extracellular vesicles, spectrin 1 INTRODUCTION Microvesicles (MV) are extracellular vesicles (EVs) measuring ∼0.1-1 μm that are shed from the plasma membrane of cells following loss of phospholipid asymmetry and cytoskeletal reorganisation [1].Plasma membrane-derived EVs are characteristic of their cell of ori-

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“…Other neuronal CaMBPs expressed in the hippocampus, such as myosin light chain kinase [ 97 , 98 ], spectrin [ 99 ], and fodrin [ 100 ], play major roles in the cytoskeleton structure and dynamics, and they also play key roles in neuronal activity and interneuronal connectivity. In addition, Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1), which is also expressed in CA1 neurons of the hippocampus, has been shown to be involved in the induction of LTP and LTD associated with spatial learning and long-term memory [ 101 , 102 ].…”

Section: The Roles Of Cam In Neurons As Cytosolic Calcium Buffering and Calcium Signaling Molecule—subcellular Distribution Of Cam-bindinmentioning

confidence: 99%

The Relevance of Amyloid β-Calmodulin Complexation in Neurons and Brain Degeneration in Alzheimer’s Disease

Poejo

Salazar

Mata

et al. 2021

IJMS

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Intraneuronal amyloid β (Aβ) oligomer accumulation precedes the appearance of amyloid plaques or neurofibrillary tangles and is neurotoxic. In Alzheimer’s disease (AD)-affected brains, intraneuronal Aβ oligomers can derive from Aβ peptide production within the neuron and, also, from vicinal neurons or reactive glial cells. Calcium homeostasis dysregulation and neuronal excitability alterations are widely accepted to play a key role in Aβ neurotoxicity in AD. However, the identification of primary Aβ-target proteins, in which functional impairment initiating cytosolic calcium homeostasis dysregulation and the critical point of no return are still pending issues. The micromolar concentration of calmodulin (CaM) in neurons and its high affinity for neurotoxic Aβ peptides (dissociation constant ≈ 1 nM) highlight a novel function of CaM, i.e., the buffering of free Aβ concentrations in the low nanomolar range. In turn, the concentration of Aβ-CaM complexes within neurons will increase as a function of time after the induction of Aβ production, and free Aβ will rise sharply when accumulated Aβ exceeds all available CaM. Thus, Aβ-CaM complexation could also play a major role in neuronal calcium signaling mediated by calmodulin-binding proteins by Aβ; a point that has been overlooked until now. In this review, we address the implications of Aβ-CaM complexation in the formation of neurotoxic Aβ oligomers, in the alteration of intracellular calcium homeostasis induced by Aβ, and of dysregulation of the calcium-dependent neuronal activity and excitability induced by Aβ.

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Axonal Spectrins: Nanoscale Organization, Functional Domains and Spectrinopathies

Cited by 28 publications

References 95 publications

Putting the axonal periodic scaffold in order

Putting the axonal periodic scaffold in order

Membrane to cytosol redistribution of αII‐spectrin drives extracellular vesicle biogenesis in malignant breast cells

The Relevance of Amyloid β-Calmodulin Complexation in Neurons and Brain Degeneration in Alzheimer’s Disease

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