Control of dendrite arborization by an Ig family member, dendrite arborization and synapse maturation 1 (Dasm1) (original) (raw)
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Molecular and Cellular Biology, 2008
The development of a highly branched dendritic tree is essential for the establishment of functional neuronal connections. The evolutionarily conserved immunoglobulin superfamily member, the protein dendrite arborization and synapse maturation 1 (Dasm-1) is thought to play a critical role in dendrite formation of dissociated hippocampal neurons. RNA interference-mediated Dasm-1 knockdown was previously shown to impair dendrite, but not axonal, outgrowth and branching (S. H. Shi, D. N. Cox, D. Wang, L. Y. Jan, and Y. N. Jan, Proc. Natl. Acad. Sci. USA 101:13341-13345, 2004). Here, we report the generation and analysis of Dasm-1 null mice. We find that genetic ablation of Dasm-1 does not interfere with hippocampal dendrite growth and branching in vitro and in vivo. Moreover, the absence of Dasm-1 does not affect the modulation of dendritic outgrowth induced by brain-derived neurotrophic factor. Importantly, the previously observed impairment in dendrite growth after Dasm-1 knockdown i...
Journal of Neuroscience, 2010
Dact1 (Dapper/Frodo), an intracellular phosphoprotein that binds Dishevelled, catenins, and other signaling proteins, is expressed in the developing and mature mammalian central nervous system, but its function there is unknown. Dact1 colocalized with synaptic markers and partitioned to postsynaptic fractions from cultured mouse forebrain neurons. Hippocampal neurons from Dact1 knockout mice had simpler dendritic arbors and fewer spines than hippocampal neurons from wild type littermates. This correlated with reductions in excitatory synapses and miniature excitatory postsynaptic currents, whereas inhibitory synapses were not affected. Loss of Dact1 resulted in a decrease in activated Rac, and recombinant expression of either Dact1 or constitutively active Rac, but not Rho or Cdc42, rescued dendrite and spine phenotypes in Dact1 mutant neurons. Our findings suggest that during neuronal differentiation Dact1 plays a critical role in a molecular pathway promoting Rac activity underlying the elaboration of dendrites and the establishment of spines and excitatory synapses.
G3 (Bethesda, Md.), 2016
Localizing messenger RNAs at specific subcellular sites is a conserved mechanism for targeting the synthesis of cytoplasmic proteins to distinct subcellular domains, thereby generating asymmetric protein distributions necessary for cellular and developmental polarity. However, the full range of transcripts that are asymmetrically distributed in specialized cell types and the significance of their localization, especially in the nervous system, are not known. We used the EP-MS2 method, which combines EP transposon insertion with the MS2/MCP in vivo fluorescent labeling system to screen for novel localized transcripts in polarized cells, focusing on the highly branched Drosophila class IV dendritic arborization neurons. Of a total of 541 lines screened, we identified 55 EP-MS2 insertions producing transcripts that were enriched in neuronal processes, particularly in dendrites. The 47 genes identified by these insertions encode molecularly diverse proteins and are enriched for genes th...
Genes & development, 2014
A complex array of genetic factors regulates neuronal dendrite morphology. Epigenetic regulation of gene expression represents a plausible mechanism to control pathways responsible for specific dendritic arbor shapes. By studying the Drosophila dendritic arborization (da) neurons, we discovered a role of the double-bromodomain and extraterminal (BET) family proteins in regulating dendrite arbor complexity. A loss-of-function mutation in the single Drosophila BET protein encoded by female sterile 1 homeotic [fs(1)h] causes loss of fine, terminal dendritic branches. Moreover, fs(1)h is necessary for the induction of branching caused by a previously identified transcription factor, Cut (Ct), which regulates subtype-specific dendrite morphology. Finally, disrupting fs(1)h function impairs the mechanosensory response of class III da sensory neurons without compromising the expression of the ion channel NompC, which mediates the mechanosensitive response. Thus, our results identify a nove...
Molecular mechanisms of dendritic spine development and remodeling
Progress in Neurobiology, 2005
Dendritic spines are small protrusions that cover the surface of dendrites and bear the postsynaptic component of excitatory synapses. Having an enlarged head connected to the dendrite by a narrow neck, dendritic spines provide a postsynaptic biochemical compartment that separates the synaptic space from the dendritic shaft and allows each spine to function as a partially independent unit. Spines develop around the time of synaptogenesis and are dynamic structures that continue to undergo remodeling over time. Changes in spine morphology and density influence the properties of neural circuits. Our knowledge of the structure and function of dendritic spines has progressed significantly since their discovery over a century ago, but many uncertainties still remain. For example, several different models have been put forth outlining the sequence of events that lead to the genesis of a spine. Although spines are small and apparently simple organelles with a cytoskeleton mainly composed of actin filaments, regulation of their morphology and physiology appears to be quite sophisticated. A multitude of molecules have been implicated in dendritic spine development and remodeling, suggesting that intricate networks of interconnected signaling pathways converge to regulate actin dynamics in spines. This complexity is not surprising, given the likely importance of dendritic spines in higher brain functions. In this review, we discuss the molecules that are currently known to mediate the exquisite sensitivity of spines to perturbations in their environment and we outline how these molecules interface with each other to mediate cascades of signals flowing from the spine surface to the actin cytoskeleton.
“Role of a Pdlim5:PalmD complex in directing dendrite morphology”
bioRxiv (Cold Spring Harbor Laboratory), 2023
Neuronal connectivity is regulated during normal brain development with the arrangement of spines and synapses being dependent on the morphology of dendrites. Further, in multiple neurodevelopmental and aging disorders, disruptions of dendrite formation or shaping is associated with atypical neuronal connectivity. We showed previously that Pdlim5 binds delta-catenin and promotes dendrite branching (Baumert et al., J Cell Biol 2020). We report here that Pdlim5 interacts with PalmD, a protein previously suggested by others to interact with the cytoskeleton (e.g., via adducin/ spectrin) and to regulate membrane shaping. Functionally, the knockdown of PalmD or Pdlim5 in rat primary hippocampal neurons dramatically reduces branching and conversely, PalmD exogenous expression promotes dendrite branching as does Pdlim5. Further, we show that each proteins' effects are dependent on the presence of the other. In summary, using primary rat hippocampal neurons we reveal the contributions of a novel Pdlim5:PalmD protein complex, composed of functionally interdependent components responsible for shaping neuronal dendrites.
CUB and Sushi multiple domains 3 regulates dendrite development
Neuroscience Research, 2016
CUB and Sushi multiple domains 3 (CSMD3) is a large protein expressed in fetal and adult brain. Recently, mutations of the CSMD3 gene were identified in schizophrenia and autism patients. However, biochemical properties and functions of the CSMD3 protein remain unknown. Here, we demonstrate that CSMD3 is an oligomeric type I transmembrane protein localized in the apical dendrites of hippocampal pyramidal neurons in the postnatal brain. In cultured hippocampal neurons, CSMD3 is expressed only after 7 days in vitro. Overexpression of CSMD3 induced dendritic branching in hippocampal neurons. Regulation of dendritic morphology by CSMD3 depended on the presence of its extracellular region, while CSMD3 intracellular region was dispensable for this activity. These results suggest that CSMD3 acts as a coreceptor of an unidentified membrane protein to regulate dendrite development. Therefore, malfunctions of CSMD3 may be one of the factors in the pathogenesis of psychiatric disorders.
CLIP-170 and IQGAP1 cooperatively regulate dendrite morphology
The Journal of …, 2011
Dendritic arbors are compartments of neurons dedicated to receiving synaptic inputs. Their shape is an outcome of both the intrinsic genetic program and environmental signals. The microtubules and actin cytoskeleton are both crucial for proper dendritic morphology, but how they interact is unclear. The present study demonstrates that microtubule plus-end tracking protein CLIP-170 and actin-binding protein IQGAP1 regulate dendrite morphology of rat neurons by coordinating the interaction between microtubules and the actin cytoskeleton. Moreover, we show that mTOR kinase interacts with CLIP-170 and is needed for efficient formation of a protein complex containing CLIP-170 and IQGAP1. Dynamic microtubules, CLIP-170, and IQGAP1 are required for proper dendritic arbor morphology and PI3K-mTOR-induced increase in dendritic arbor complexity. Moreover, CLIP-170 and IQGAP1 knockdown modulates dendritic arbor growth via regulation of the actin cytoskeleton. We postulate that mTOR controls dendritic arbor morphology by enhancing cross talk between dynamic microtubules and actin through CLIP-170 and IQGAP1.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012
Integrins are heterodimeric extracellular matrix receptors that are essential for the proper development of the vertebrate nervous system. We report here that selective loss of integrin β1 in excitatory neurons leads to reductions in the size and complexity of hippocampal dendritic arbors, hippocampal synapse loss, impaired hippocampus-dependent learning, and exaggerated psychomotor sensitivity to cocaine in mice. Our biochemical and genetic experiments demonstrate that the intracellular tail of integrin β1 binds directly to Arg kinase and that this interaction stimulates activity of the Arg substrate p190RhoGAP, an inactivator of the RhoA GTPase. Moreover, genetic manipulations that reduce integrin β1 signaling through Arg recapitulate the integrin β1 knock-out phenotype in a gene dose-sensitive manner. Together, these results describe a novel integrin β1-Arg-p190RhoGAP pathway that regulates dendritic arbor size, promotes synapse maintenance, supports proper hippocampal function, ...
FEZ1 Forms Complexes with CRMP1 and DCC to Regulate Axon and Dendrite Development
ENeuro, 2021
Elaboration of neuronal processes is an early step in neuronal development. Guidance cues must work closely with intracellular trafficking pathways to direct expanding axons and dendrites to their target neurons during the formation of neuronal networks. However, how such coordination is achieved remains incompletely understood. Here, we characterize an interaction between fasciculation and elongation protein zeta 1 (FEZ1), an adapter involved in synaptic protein transport, and collapsin response mediator protein (CRMP)1, a protein that functions in growth cone guidance, at neuronal growth cones. We show that similar to CRMP1 loss-of-function mutants, FEZ1 deficiency in rat hippocampal neurons causes growth cone collapse and impairs axonal development. Strikingly, FEZ1-deficient neurons also exhibited a reduction in dendritic complexity stronger than that observed in CRMP1-deficient neurons, suggesting that the former could partake in additional developmental signaling pathways. Supporting this, FEZ1 colocalizes with VAMP2 in developing hippocampal neurons and forms a separate complex with deleted in colorectal cancer (DCC) and Syntaxin-1 (Stx1), components of the Netrin-1 signaling pathway that are also involved in regulating axon and dendrite development. Significantly, developing axons and dendrites of FEZ1-deficient neurons fail to respond to Netrin-1 or Netrin-1 and Sema3A treatment, respectively. Taken together, these findings highlight the importance of FEZ1 as a common effector to integrate guidance signaling pathways with intracellular trafficking to mediate axo-dendrite development during neuronal network formation.