Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology

Kim, Yong; Sung, Jee Young; Ceglia, Ilaria; Lee, Ko Woon; Ahn, Jung Ja; Halford, Jonathan M.; Kim, Amie M.; Kwak, Seung; Park, Jong Bae; Ryu, Sung Ho; Schenck, Annette; Bardoni, Barbara; Scott, John D.; Nairn, Angus C.; Greengard, Paul

doi:10.1038/nature04976

Cited by 280 publications

(321 citation statements)

References 24 publications

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“…As the morphology of the Golgi complex depends to a large extent on the integrity of the surrounding cytoskeletal elements (Bard and Malhotra, 2006;Egea et al, 2006;De Matteis and Luini, 2008), the observed disruption of the Golgi complex could be also a consequence of altered cytoskeletal organization upon kdPKD1 expression. Additionally, cytoskeletal rearrangements fundamentally influence the formation and maintenance of dendritic structures, including elongation and branching of dendrites or spine formation (Gauthier-Campbell et al, 2004;Kim et al, 2006;Hayashi et al, 2007;Tada et al, 2007;Zhang and Macara, 2008). Accordingly, direct or indirect cytoskeletal effects of PKD can also participate in the observed dendritic rearrangements in transfected neurons, especially when taking into account that high level of PKD activity was observed not only around the neuronal Golgi but also in the cytoplasm of dendrites and even in the dendritic spines.…”

Section: Discussionmentioning

confidence: 99%

Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

Czöndör

Ellwanger²,

Fuchs³

et al. 2009

MBoC

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Protein kinase D (PKD) is known to participate in various cellular functions, including secretory vesicle fission from theGolgi and plasma membrane-directed transport. Here, we report on expression and function of PKD in hippocampal neurons. Expression of an enhanced green fluorescent protein (EGFP)-tagged PKD activity reporter in mouse embryonal hippocampal neurons revealed high endogenous PKD activity at the Golgi complex and in the dendrites, whereas PKD activity was excluded from the axon in parallel with axonal maturation. Expression of fluorescently tagged wild-type PKD1 and constitutively active PKD1 S738/742E (caPKD1) in neurons revealed that both proteins were slightly enriched at the trans-Golgi network (TGN) and did not interfere with its thread-like morphology. By contrast, expression of dominant-negative kinase inactive PKD1 K612W (kdPKD1) led to the disruption of the neuronal Golgi complex, with kdPKD1 strongly localized to the TGN fragments. Similar findings were obtained from transgenic mice with inducible, neuron-specific expression of kdPKD1-EGFP. As a prominent consequence of kdPKD1 expression, the dendritic tree of transfected neurons was reduced, whereas caPKD1 increased dendritic arborization. Our results thus provide direct evidence that PKD activity is selectively involved in the maintenance of dendritic arborization and Golgi structure of hippocampal neurons. INTRODUCTIONNeurons are nondividing and extremely polarized cells, with enormous membrane surface compared with the size of the soma. These features assume a highly specialized secretory machinery, which resembles in certain parts the directed transport mechanisms described in polarized nonneuronal cells (Winckler and Mellman, 1999;Horton and Ehlers, 2004). The vast neuronal membrane surface is functionally and structurally divided into axonal and somatodendritic compartments, possessing specific lipid and protein components required for the spatially different functions, e.g., for pre-or postsynaptic activity (Dresbach et al., 2001;Sheng, 2001;Bresler et al., 2004). The constitutive and precisely directed supply of surface membrane components is indispensable for the function of neurons, especially when considering that postmitotic neurons normally serve throughout the life span of the organism. Up to now, we are far from understanding how the extreme polarization has been evolved and is maintained in neurons.Despite a likely central role in neuronal morphogenesis and membrane trafficking, little is known about the special structure and transport features of the neuronal Golgi apparatus. A thread-like and reticular structure of the Golgi apparatus has been already described in many neuronal types (Takamine et al., 2000;Fujita and Okamoto, 2005;Horton et al., 2005). Central neuronal Golgi complex is localized in the soma and often extends into the principal dendrites, but Golgi elements were also found as discontinuous structures in the distal dendrites, often near synaptic contacts or in dendritic spines (Gardiol et al., 1999;Pierc...

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Section: Discussionmentioning

confidence: 99%

Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

Czöndör

Ellwanger²,

Fuchs³

et al. 2009

MBoC

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“…The WRC triggers N-WASP-dependent activation of actin-related protein (Arp)-2/3-dependent actin nucleation 57,58 , which controls actin filament rearrangements connected to dendritic spine formation, retraction, motility, structure and stability 59 . Disturbing WRC function by genetic ablation of the WRC components therefore alters dendritic spine structure and affects excitability [60][61][62] . CYFIP1 is highly enriched at synapses and its expression level is important for correct dendritic arborization and neuronal morphological complexity.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…When active Rac-GTP is added, the complex dissociates, freeing WAVE1 and HSPC 300, allowing WAVE1 to activate the actin-related protein 2/3 (Arp2/3) complex to induce actin polymerization. Interestingly, recent studies have demonstrated a critical role for phosphorylated WAVE1 in dendritic spine morphogenesis through its effect on the actin cytoskeleton [47].…”

Section: Fragile-x Syndromementioning

confidence: 99%

Rho-linked genes and neurological disorders

Kasri

Aelst

2007

Pflugers Arch - Eur J Physiol

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Mental retardation (MR) is a common cause of intellectual disability and affects approximately 2 to 3 % of children and young adults. MR has been consistently associated with changes in dendrites and dendritic spine structure. Given that dendritic spine morphology has been tightly linked to synaptic activity, altered spine morphology has been suggested to be the underlying cause of cognitive disabilities observed in MR. The structure and dynamics of dendritic spines is determined by its underlying actin cytoskeleton. Signaling molecules and cascades important for cytoskeletal regulation have therefore naturally attracted a great deal of attention. As key regulators of both the actin and microtubule cytoskeletons, it is not surprising that the Rho GTPases have emerged as important regulators of dendrite and spine structural plasticity. In support of this, mutations in regulators and effectors of Rho GTPases have been associated with diseases affecting the nervous system, including MR and amyotropic lateral sclerosis (ALS). Here we will discuss Rho GTPase related genes and their signaling pathways involved in MR and ALS.

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Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology

Cited by 280 publications

References 24 publications

Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

Dendritic spine actin cytoskeleton in autism spectrum disorder

Rho-linked genes and neurological disorders

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