Topic: microtubules

In our research, we delve into the intricacies of neuronal structure and function, focusing on the crucial roles of axonal transport and localized protein synthesis for maintaining neuronal communication and overall health. Neurons rely on axonal transport to move organelles, proteins, and mRNAs across their extensive dendritic and axonal networks, a process facilitated by molecular motors traveling along microtubules. This is essential for cellular equilibrium and, when disrupted, is often linked to neurological diseases. We particularly explore the regulation of microtubule dynamics through

Background: Activity-dependent neuroprotective protein (ADNP) is crucial for chromatin/cytoskeletal functions. ADNP deregulation is linked to neurodevelopmental/neurodegenerative/psychiatric diseases. Mutations in ADNP cause the ADNP syndrome and parallel tauopathy in Alzheimer’. We showed aberrant nuclear-cytoplasmic distribution in ADNP-mutated neuronal-like cells, which was corrected by the ADNP-derived fragment, NAP (Cells, 2022). Here we asked what is the mechanism in which NAP corrects the aberrant distribution. Methods: CRISPR/Cas9 genome-editing established N1E-115 neuroblastoma cell l

Tau, is an intrinsically disordered protein crucial for stabilizing and polymerizing microtubules (MTs). However, in Alzheimer's disease (AD), Tau undergoes hyperphosphorylation, leading to its misfolding and detachment from MTs, forming droplets termed liquid-liquid phase separation (LLPS), believed to be a precursor to Tau aggregates. Despite being a biomarker for AD, the role of AT8 phosphorylation (S202, T205, and S208) in Tau spread and toxicity remains unclear. To address this issue, we generated Tau variants with different AT8 phosphorylation states: PTau 2A-, 208- (lacking AT8 phosphor

Autophagy is a fundamental cellular process that plays a role in many physiological and pathophysiological processes. Microtubules are dynamic cytoskeletal fibers composed of tubulin dimers that have diverse structure and functions in cells. They are notably involved in cellular trafficking and autophagosome formation. The detyrosination/tyrosination cycle, a post-translational modification of tubulin, controls microtubule functions in healthy neurons, and its dysregulations lead to neuronal defects. This cycle is characterized by the enzymatic removal and re-addition of a gene-encoded tyrosin

Tau accumulation is clearly linked to pathogenesis in Alzheimer’s disease and other Tauopathies. However, processes leading to Tau fibrillization and reasons for its pathogenicity remain largely elusive. Mical emerged as a novel interacting protein of human Tau expressed in Drosophila brains. Mical is characterized by the presence of a flavoprotein monooxygenase domain that generates redox potential with which it can oxidize target proteins. In the well-established Drosophila Tauopathy model, we use genetic interactions to show that Mical alters Tau interactions with microtubules and the Actin

Microtubules are key to multiple neuronal functions involving the transport of organelles, however, their relationship to neurotransmitter release is still unresolved. Here, we show that microtubules present in the presynaptic compartment of cholinergic autaptic synapses are dynamic. To investigate how the balance between microtubule growth and shrinkage affects neurotransmission we induced synchronous microtubule depolymerization by photoactivation of the chemical inhibitor SBTub3. The consequence was an increase in spontaneous neurotransmitter release. An analogous effect was obtained by dia

The axonal initial segment (AIS) is a crucial neuronal subdomain that coordinates the axo-dendritic polarity establishment and maintenance and constitutes the site for action potential (AP) initiation. Its integrity relies on proteins like AnkyrinG (AnkG) which, by organizing the cytoskeleton, anchor the ionic channels necessary for AP generation. Many AIS proteins are linked to neurodevelopmental disorders (NDD) like epilepsy or autism and the AIS proteome deciphering is warranted to provide insight into novel therapeutic targets for the treatment of human diseases of the nervous system.Plana

Neurons are characterised by their intricate polarised morphology, crucial for proper CNS function. Achieving and maintaining this morphology is essential, facilitated by microtubules, key constituents of the neuronal cytoskeleton. Microtubule function is modulated by Microtubule Associated Proteins (MAPs), among which microtubule-stabilising MAP6d1 stands out for being the first neuronal protein identified to be directly involved in the formation of microtubule doublets in vitro. Microtubule doublets are highly stable structures specifically crucial for the formation and functioning of cilia

Second harmonic imaging is a non-linear optical process that relies on the interaction of 2 photons with the sample. In this interaction, a photon of half the wavelength of the initial incoming light is generated. The generation of second harmonic signals requires the sample to have non-centrosymmetric molecular organization. Microtubules are composed of polymerized tubulin dimers and they are a major component in the cytoskeleton of neurons. Axons, in particular, have unipolarized microtubules with the plus ends growing away from the soma. This leads to an aligned microtubule organization in

Neural network formation throughout development and regeneration after injury depends on accuracy of axonal pathfinding, which is influenced by chemical and physical cues. Recently, there is growing evidence that local temperature fluctuations in the brain play a crucial role in axonal guidance. However, the precise mechanisms involved in this process are not completely understood. We hypothesize that spontaneous and trauma-induced axon growth is repelled by increasing nanoscale temperature gradients leading to growth inhibition and growth cone retraction. Transient receptor potential vanilloi

Microtubules play a crucial role in dendritic and axonal physiology through acting as railroad tracks on which numerous factors are transported. More than one hundred microtubules in a neurite form a large array that changes in composition during the development of dendrites and the axon. Throughout development, this large array was long thought to act as the stationary backbone of neurons. In contrast, we recently made the surprising discovery that the microtubule array in fact constantly moves towards the soma as a whole. This microtubule retrograde flow (MT-RF) destabilizes neurite growth.

The presence and roles of tubulin in and around the postsynaptic density (PSD) has long been a point of debate, despite the identification of tubulin immunoreactivity in the PSD as early as 1975. In our previous paper (Suzuki et al., 2021, Life Science Alliance, 4; e202000945) we have suggested a fundamental role for tubulin in the structure of the postsynaptic density (PSD) at excitatory synapses based on our experiments on PSD lattice (PSDL), which is an backbone structure for PSD. This investigation extends our prior exploration of the PSDL, and unveils a hitherto unrecognized characteristi