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Progress in Neurobiology Dec 2023Dendritic spines are key structures for neural communication, learning and memory. Spine size and shape probably reflect synaptic strength and learning. Imaging with...
Dendritic spines are key structures for neural communication, learning and memory. Spine size and shape probably reflect synaptic strength and learning. Imaging with superresolution STED microscopy the detailed shape of the majority of the spines of individual neurons in turtle cortex (Trachemys scripta elegans) revealed several distinguishable shape classes. Dendritic spines of a given class were not distributed randomly, but rather decorated significantly more often some dendrites than others. The individuality of dendrites was corroborated by significant inter-dendrite differences in other parameters such as spine density and length. In addition, many spines were branched or possessed spinules. These findings may have implications for the role of individual dendrites in this cortex.
Topics: Animals; Dendrites; Turtles; Microscopy; Neurons; Cerebral Cortex; Dendritic Spines
PubMed: 37898315
DOI: 10.1016/j.pneurobio.2023.102541 -
Proceedings of the National Academy of... Oct 2021How signaling units spontaneously arise from a noisy cellular background is not well understood. Here, we show that stochastic membrane deformations can nucleate...
How signaling units spontaneously arise from a noisy cellular background is not well understood. Here, we show that stochastic membrane deformations can nucleate exploratory dendritic filopodia, dynamic actin-rich structures used by neurons to sample its surroundings for compatible transcellular contacts. A theoretical analysis demonstrates that corecruitment of positive and negative curvature-sensitive proteins to deformed membranes minimizes the free energy of the system, allowing the formation of long-lived curved membrane sections from stochastic membrane fluctuations. Quantitative experiments show that once recruited, curvature-sensitive proteins form a signaling circuit composed of interlinked positive and negative actin-regulatory feedback loops. As the positive but not the negative feedback loop can sense the dendrite diameter, this self-organizing circuit determines filopodia initiation frequency along tapering dendrites. Together, our findings identify a receptor-independent signaling circuit that employs random membrane deformations to simultaneously elicit and limit formation of exploratory filopodia to distal dendritic sites of developing neurons.
Topics: Animals; Dendrites; Neurons; Pseudopodia; Signal Transduction; Stochastic Processes
PubMed: 34686599
DOI: 10.1073/pnas.2106921118 -
Cerebral Cortex (New York, N.Y. : 1991) Oct 2000Proper growth and branching of dendrites are crucial for nervous system function; patterns of dendritic arborization determine the nature and amount of innervation that... (Review)
Review
Proper growth and branching of dendrites are crucial for nervous system function; patterns of dendritic arborization determine the nature and amount of innervation that a neuron receives and specific dendritic membrane properties define its computational capabilities. Until recently, there was relatively little known about the cellular and molecular mechanisms of dendritic growth, perhaps because dendrites were historically considered to be intrinsically determined, passive elements in the formation of connections in the nervous system. In the last few years, however, overwhelming evidence has accumulated indicating that dendritic growth is remarkably dynamic and responsive to environmental signals, including guidance molecules and levels and patterns of activity. This manuscript reviews our current understanding of the cellular and molecular mechanisms of dendritic growth, the influence of activity in sculpting specific patterns of dendritic arbors, and a potential integral role for dendrites in activity-dependent development of circuits in the nervous system.
Topics: Animals; Dendrites; Extracellular Space; Humans; Intracellular Fluid; Models, Neurological; Nerve Tissue Proteins; Signal Transduction; Synapses
PubMed: 11007547
DOI: 10.1093/cercor/10.10.963 -
The International Journal of... Nov 2013The Abl2/Arg nonreceptor tyrosine kinase is enriched in dendritic spines where it is essential for maintaining dendrite and synapse stability in the postnatal mouse... (Review)
Review
The Abl2/Arg nonreceptor tyrosine kinase is enriched in dendritic spines where it is essential for maintaining dendrite and synapse stability in the postnatal mouse brain. Arg is activated downstream of integrin α3β1 receptors and it regulates the neuronal actin cytoskeleton by directly binding F-actin and via phosphorylation of substrates including p190RhoGAP and cortactin. Neurons in mice lacking Arg or integrin α3β1 develop normally through postnatal day 21 (P21), however by P42 mice exhibit major reductions in dendrite arbor size and complexity, and lose dendritic spines and synapses. As a result, mice with loss of Arg and Arg-dependent signaling pathways have impairments in memory tasks, heightened sensitivity to cocaine, and vulnerability to corticosteroid-induced neuronal remodeling. Therefore, understanding the molecular mechanisms of Arg regulation may lead to therapeutic approaches to treat human psychiatric and neurodegenerative diseases in which neuronal structure is destabilized.
Topics: Animals; Cocaine; Dendrites; Humans; Memory; Protein-Tyrosine Kinases; Signal Transduction; Stress, Psychological; Synapses
PubMed: 23916785
DOI: 10.1016/j.biocel.2013.07.018 -
Cold Spring Harbor Perspectives in... Sep 2010The spatial pattern of branches within axonal or dendritic arbors and the relative arrangement of neighboring arbors with respect to one another impact a neuron's... (Review)
Review
The spatial pattern of branches within axonal or dendritic arbors and the relative arrangement of neighboring arbors with respect to one another impact a neuron's potential connectivity. Although arbors can adopt diverse branching patterns to suit their functions, evenly spread branches that avoid clumping or overlap are a common feature of many axonal and dendritic arbors. The degree of overlap between neighboring arbors innervating a surface is also characteristic within particular neuron types. The arbors of some populations of neurons innervate a target with a comprehensive and nonoverlapping "tiled" arrangement, whereas those of others show substantial territory overlap. This review focuses on cellular and molecular studies that have provided insight into the regulation of spatial arrangements of neurite branches within and between arbors. These studies have revealed principles that govern arbor arrangements in dendrites and axons in both vertebrates and invertebrates. Diverse molecular mechanisms controlling the spatial patterning of sister branches and neighboring arbors have begun to be elucidated.
Topics: Animals; Axons; Dendrites; Humans; Models, Neurological; Nerve Net; Neurons
PubMed: 20573716
DOI: 10.1101/cshperspect.a001750 -
Neuron Jan 2002The cellular and molecular mechanisms that guide axonal and dendritic differentiation in the cerebral cortex are just beginning to be defined. Many of the molecular... (Review)
Review
The cellular and molecular mechanisms that guide axonal and dendritic differentiation in the cerebral cortex are just beginning to be defined. Many of the molecular signals that guide axons also, and sometimes simultaneously, influence dendritic growth. Whitford et al. (2002 [this issue of Neuron]) demonstrate that in addition to their roles in axon guidance and cell migration cue, Slit proteins can also regulate dendritic growth.
Topics: Animals; Carrier Proteins; Cell Differentiation; Cerebral Cortex; Chemotaxis; Dendrites; Growth Cones; Humans; Nerve Tissue Proteins; Receptors, Immunologic; Semaphorin-3A; Roundabout Proteins
PubMed: 11779471
DOI: 10.1016/s0896-6273(01)00577-3 -
Biochimica Et Biophysica Acta Feb 2008Polarized growth of the neuron would logically require some form of membrane traffic to the tip of the growth cone, regulated in conjunction with other trafficking... (Review)
Review
Polarized growth of the neuron would logically require some form of membrane traffic to the tip of the growth cone, regulated in conjunction with other trafficking processes that are common to both neuronal and non-neuronal cells. Unlike axons, dendrites are endowed with membranous organelles of the exocytic pathway extending from the cell soma, including both rough and smooth endoplasmic reticulum (ER) and the ER-Golgi intermediate compartment (ERGIC). Dendrites also have satellite Golgi-like cisternal stacks known as Golgi outposts that have no membranous connections with the somatic Golgi. Golgi outposts presumably serve both general and specific local trafficking needs, and could mediate membrane traffic required for polarized dendritic growth during neuronal differentiation. Recent findings suggest that dendritic growth, but apparently not axonal growth, relies very much on classical exocytic traffic, and is affected by defects in components of both the early and late secretory pathways. Within dendrites, localized processes of recycling endosome-based exocytosis regulate the growth of dendritic spines and postsynaptic compartments. Emerging membrane traffic processes and components that contribute specifically to dendritic growth are discussed.
Topics: Animals; Biological Transport; Dendrites; Exocytosis; Humans; Intracellular Membranes; trans-Golgi Network
PubMed: 18155172
DOI: 10.1016/j.bbamcr.2007.11.011 -
The Journal of Cell Biology Oct 2018The actin cytoskeleton provides structural stability and adaptability to the cell. Neuronal dendrites frequently undergo morphological changes by emanating, elongating,...
The actin cytoskeleton provides structural stability and adaptability to the cell. Neuronal dendrites frequently undergo morphological changes by emanating, elongating, and withdrawing branches. However, the knowledge about actin dynamics in dendrites during these processes is limited. By performing in vivo imaging of F-actin markers, we found that F-actin was highly dynamic and heterogeneously distributed in dendritic shafts with enrichment at terminal dendrites. A dynamic F-actin population that we named actin blobs propagated bidirectionally at an average velocity of 1 µm/min. Interestingly, these actin blobs stalled at sites where new dendrites would branch out in minutes. Overstabilization of F-actin by the G15S mutant abolished actin blobs and dendrite branching. We identified the F-actin-severing protein Tsr/cofilin as a regulator of dynamic actin blobs and branching activity. Hence, actin blob localization at future branching sites represents a dendrite-branching mechanism to account for highly diversified dendritic morphology.
Topics: Actins; Amino Acid Substitution; Animals; Dendrites; Drosophila Proteins; Drosophila melanogaster; Mutation, Missense
PubMed: 30042190
DOI: 10.1083/jcb.201711136 -
Current Opinion in Neurobiology Jun 2003During development, the nervous system is confronted with a problem of enormous complexity; to progress from a large number of 'disconnected' neurons to a network of... (Review)
Review
During development, the nervous system is confronted with a problem of enormous complexity; to progress from a large number of 'disconnected' neurons to a network of neuronal circuitry that is able to dynamically process sensory information and generate an appropriate output. To form these circuits, growing axons must make synapses with targets, usually the dendrites of postsynaptic neurons. Although a significant amount is known about the signals that regulate and guide developing axons, we are only now starting to understand how environmental cues like growth factors and activity regulate the formation and maintenance of dendrites in the developing and mature nervous system.
Topics: Animals; Dendrites; Humans; Signal Transduction
PubMed: 12850225
DOI: 10.1016/s0959-4388(03)00072-2 -
FASEB Journal : Official Publication of... Jan 2022Proper dendritic morphology is fundamental to nerve signal transmission; thus, revealing the mechanism by which dendrite arborization is regulated is of great...
Proper dendritic morphology is fundamental to nerve signal transmission; thus, revealing the mechanism by which dendrite arborization is regulated is of great significance. Our previous studies have found that the epigenetic molecule chromodomain Y-like (CDYL) negatively regulates dendritic branching. Current research mostly focuses on the processes downstream of CDYL, whereas the upstream regulatory process has not been investigated to date. In this study, we identified an upstream regulator of CDYL, the E3 ubiquitin ligase tripartite motif-containing protein 32 (TRIM32), which promotes dendrite arborization by mediating the ubiquitylation and degradation of CDYL. By using mass spectrometry and biochemistry strategies, we proved that TRIM32 interacted with CDYL and mediated CDYL ubiquitylation modification in vivo and in vitro. Overexpressing TRIM32 decreased the protein level of CDYL, leading to an increase in the dendritic complexity of primary cultured rat neurons. In contrast, knocking down TRIM32 increased the protein level of CDYL and decreased the dendritic complexity. The truncated form of TRIM32 without E3 ligase activity (ΔRING) lost its ability to regulate dendritic complexity. Most importantly, knockdown of CDYL abolished the reduced complexity of dendrites caused by TRIM32 knockdown, indicating that the TRIM32-mediated regulation of dendritic development depends on its regulation of downstream CDYL. Hence, our findings reveal that TRIM32 could promote dendrite arborization by mediating CDYL degradation. This work initially defines a novel biological role of TRIM32 in regulating mechanisms upstream of CDYL and further presents a potential therapeutic target for the treatment of CDYL-related neurodevelopmental disorders.
Topics: Animals; Co-Repressor Proteins; Dendrites; Male; Proteolysis; Rats; Rats, Sprague-Dawley; Transcription Factors; Tripartite Motif Proteins; Ubiquitin-Protein Ligases; Ubiquitination
PubMed: 34888944
DOI: 10.1096/fj.202100031RR