Cobl-like promotes actin filament formation and dendritic branching using only a single WH2 domain

Izadi, Maryam; Schlobinski, Dirk; Lahr, Maria; Schwintzer, Lukas; Qualmann, Britta; Kessels, Michael M.

doi:10.1083/jcb.201704071

Cited by 23 publications

(33 citation statements)

References 42 publications

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“…In contrast, both PHLDB2 and COBLL1 are highly expressed in COL22A1 and CARM1P1 t-types, with PHLDB2 displaying slightly more specific enrichment of expression in these t-types. COBLL1 is a morphogenesis-associated gene that has been shown to promote dendrite branching and the formation of actin filament membrane ruffles 45 . Similarly, PHLDB2 localizes to dendritic spines of hippocampal neurons where it plays an important role in regulation of long-term potentiation by affecting the density of glutamate receptors, and knockout of this gene impairs the formation of memories in mice 46 .…”

Section: Resultsmentioning

confidence: 99%

Human cortical expansion involves diversification and specialization of supragranular intratelencephalic-projecting neurons

Berg

Sorensen

Ting

et al. 2020

Preprint

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The neocortex is disproportionately expanded in human compared to mouse, both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers that selectively make connections within the cortex and other telencephalic structures. Single-cell transcriptomic analyses of human and mouse cortex show an increased diversity of glutamatergic neuron types in supragranular cortex in human and pronounced gradients as a function of cortical depth. To probe the functional and anatomical correlates of this transcriptomic diversity, we describe a robust Patch-seq platform using neurosurgically-resected human tissues. We characterize the morphological and physiological properties of five transcriptomically defined human glutamatergic supragranular neuron types. Three of these types have properties that are specialized compared to the more homogeneous properties of transcriptomically defined homologous mouse neuron types. The two remaining supragranular neuron types, located exclusively in deep layer 3, do not have clear mouse homologues in supragranular cortex but are transcriptionally most similar to deep layer mouse intratelencephalic-projecting neuron types. Furthermore, we reveal the transcriptomic types in deep layer 3 that express high levels of non-phosphorylated heavy chain neurofilament protein that label long-range neurons known to be selectively depleted in Alzheimer’s disease. Together, these results demonstrate the power of transcriptomic cell type classification, provide a mechanistic underpinning for increased complexity of cortical function in human cortical evolution, and implicate discrete transcriptomic cell types as selectively vulnerable in disease.

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Section: Resultsmentioning

confidence: 99%

Human cortical expansion involves diversification and specialization of supragranular intratelencephalic-projecting neurons

Berg

Sorensen

Ting

et al. 2020

Preprint

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“…Primary rat hippocampal neuronal cells for immunofluorescence analyzes were cultured and maintained as described previously [ 30 , 31 , 32 ]. Briefly, neurons dissociated from hippocampi of E18 rats were seeded at a density of 60,000/well (24-well plate).…”

Section: Methodsmentioning

confidence: 99%

Comparison of Multiscale Imaging Methods for Brain Research

Tröger

Hoischen

Perner

et al. 2020

Cells

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A major challenge in neuroscience is how to study structural alterations in the brain. Even small changes in synaptic composition could have severe outcomes for body functions. Many neuropathological diseases are attributable to disorganization of particular synaptic proteins. Yet, to detect and comprehensively describe and evaluate such often rather subtle deviations from the normal physiological status in a detailed and quantitative manner is very challenging. Here, we have compared side-by-side several commercially available light microscopes for their suitability in visualizing synaptic components in larger parts of the brain at low resolution, at extended resolution as well as at super-resolution. Microscopic technologies included stereo, widefield, deconvolution, confocal, and super-resolution set-ups. We also analyzed the impact of adaptive optics, a motorized objective correction collar and CUDA graphics card technology on imaging quality and acquisition speed. Our observations evaluate a basic set of techniques, which allow for multi-color brain imaging from centimeter to nanometer scales. The comparative multi-modal strategy we established can be used as a guide for researchers to select the most appropriate light microscopy method in addressing specific questions in brain research, and we also give insights into recent developments such as optical aberration corrections.

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“…The actin nucleator Cobl and its evolutionary ancestor protein Cobl-like are molecularly quite distinct ( Figure 1–figure supplement 1 ), however, both critical for dendritic arbor formation (Ahuja et al, 2007; Izadi et al, 2018). Side-by-side loss-of-function analysis of both factors in developing primary hippocampal neurons using IMARIS software-based evaluations for detailed analyses of the elaborate morphology of such cells (Izadi et al, 2018) revealed surprisingly similar phenotypes ( Figure 1A-G ). Dendritic branch and terminal point numbers as well as total dendritic length all were severely affected by lack of Cobl-like ( Figure 1A-G ).…”

Section: Resultsmentioning

confidence: 99%

“…We next addressed whether the identified Cobl-like interaction partner syndapin I would indeed be critical for Cobl-like’s functions. GFP-Cobl-like massively promoted dendritic arborization already after very short times (Izadi et al, 2018). Strikingly, all Cobl-like gain-of-function phenotypes in developing primary hippocampal neurons were completely suppressed upon syndapin I RNAi ( Figure 4C ).…”

Section: Resultsmentioning

confidence: 99%

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Functional interdependence of the actin nucleator Cobl and Cobl-like in dendritic arbor development

Izadi

Seemann

Schlobinski

et al. 2021

Preprint

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Local actin filament formation is indispensable for development of the dendritic arbor of neurons. We show that, surprisingly, the action of single actin filament-promoting factors was insufficient for powering dendritogenesis. Instead, this process required the actin nucleator Cobl and its only evolutionary distant ancestor Cobl-like acting interdependently. This coordination between Cobl-like and Cobl was achieved by physical linkage by syndapin I. Syndapin I formed nanodomains at convex plasma membrane areas at the base of protrusive structures and interacted with three motifs in Cobl-like, one of which was Ca2+/calmodulin-regulated. Consistently, syndapin I, Cobl-like’s newly identified N terminal calmodulin-binding site and the single Ca2+/calmodulin-responsive syndapin-binding motif all were critical for Cobl-like’s functions. In dendritic arbor development, local Ca2+/CaM-controlled actin dynamics thus relies on regulated and physically coordinated interactions of different F-actin formation-promoting factors and only together they have the power to bring about the sophisticated neuronal morphologies required for neuronal network formation.

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Cobl-like promotes actin filament formation and dendritic branching using only a single WH2 domain

Cited by 23 publications

References 42 publications

Human cortical expansion involves diversification and specialization of supragranular intratelencephalic-projecting neurons

Human cortical expansion involves diversification and specialization of supragranular intratelencephalic-projecting neurons

Comparison of Multiscale Imaging Methods for Brain Research

Functional interdependence of the actin nucleator Cobl and Cobl-like in dendritic arbor development

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