The Actin Nucleator Cobl Is Crucial for Purkinje Cell Development and Works in Close Conjunction with the F-Actin Binding Protein Abp1

Haag, Natja; Schwintzer, Lukas; Ahuja, Rashmi; Koch, Nicole; Grimm, Julia; Heuer, Heike; Qualmann, Britta; Kessels, Michael M.

doi:10.1523/jneurosci.0843-12.2012

Cited by 47 publications

(82 citation statements)

References 33 publications

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“…Spir proteins belong to a family of actin nucleators that includes Cordon-bleu (Cobl) and Junction-mediating and regulatory protein (JMY). Knockdown of Cobl reduced dendrite branching complexity in cultures of rat hippocampal neurons (Ahuja et al, 2007), and in Purkinje neurons in organotypic slices of mouse cerebellum (Haag et al, 2012), while JMY knockdown in mouse neuroblastoma cells enhanced neurite outgrowth (Firat-Karalar et al, 2011). Future experiments will determine whether and how Cobl, JMY and Spir proteins influence dendrite arborization in the mammalian brain.…”

Section: Discussionmentioning

confidence: 98%

Dendrite architecture organized by transcriptional control of the F-actin nucleator Spire

Ferreira

et al. 2014

Development

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The architectures of dendritic trees are crucial for the wiring and function of neuronal circuits because they determine coverage of receptive territories, as well as the nature and strength of sensory or synaptic inputs. Here, we describe a cell-intrinsic pathway sculpting dendritic arborization (da) neurons in Drosophila that requires Longitudinals Lacking (Lola), a BTB/POZ transcription factor, and its control of the F-actin cytoskeleton through Spire (Spir), an actin nucleation protein. Loss of Lola from da neurons reduced the overall length of dendritic arbors, increased the expression of Spir, and produced inappropriate F-actin-rich dendrites at positions too near the cell soma. Selective removal of Lola from only class IV da neurons decreased the evasive responses of larvae to nociception. The increased Spir expression contributed to the abnormal F-actinrich dendrites and the decreased nocifensive responses because both were suppressed by reduced dose of Spir. Thus, an important role of Lola is to limit expression of Spir to appropriate levels within da neurons. We found Spir to be expressed in dendritic arbors and to be important for their development. Removal of Spir from class IV da neurons reduced F-actin levels and total branch number, shifted the position of greatest branch density away from the cell soma, and compromised nocifensive behavior. We conclude that the Lola-Spir pathway is crucial for the spatial arrangement of branches within dendritic trees and for neural circuit function because it provides balanced control of the F-actin cytoskeleton.

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Section: Discussionmentioning

confidence: 98%

Dendrite architecture organized by transcriptional control of the F-actin nucleator Spire

Ferreira

et al. 2014

Development

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“…The use of distinct promoters excludes that reduced RNAi effects caused by exhaustion of endogenous factors associating with two instead of one plasmid feign a putative phenotype suppression. The additional use of two different fluorescent reporters (GFP and PM-mCherry, respectively) ensured that double-transfection of neurons can be validated (Haag et al 2012). Cotransfection of hippocampal neurons with FMRP RNAi and p0071 RNAi effectively suppressed the promotion of dendritogenesis observed upon knocking down FMRP alone.…”

Section: P0071 and Fmrp Modulate Neurite Outgrowth And Dendritic Arbomentioning

confidence: 99%

“…A scrambled RNAi control driven by the U6.1 promoter (scrambled RNAi1 in pRNAT-U6.1 PM-mCherry ; scr. RNAi PM-mCherry ) was generated by replacing GFP with PM-mCherry in scrambled RNAi GFP (U6.1) (Haag et al 2012). …”

Section: -Gatcccacagcgtctgaacgtagtttcaagagaactacgttcmentioning

confidence: 99%

FMRP regulates actin filament organization via the armadillo protein p0071

Nolze

Schneider

Keil

et al. 2013

RNA

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Loss of fragile X mental retardation protein (FMRP) causes synaptic dysfunction and intellectual disability. FMRP is an RNAbinding protein that controls the translation or turnover of a subset of mRNAs. Identifying these target transcripts is an important step toward understanding the pathology of the disease. Here, we show that FMRP regulates actin organization and neurite outgrowth via the armadillo protein p0071. In mouse embryonic fibroblasts (MEFs) lacking FMRP (Fmr1−), the actin cytoskeleton was markedly reorganized with reduced stress fibers and F-actin/G-actin ratios compared to fibroblasts reexpressing the protein. FMRP interfered with the translation of the p0071 mRNA in a 3 ′ -UTR-dependent manner. Accordingly, FMRP-depleted cells revealed elevated levels of p0071 protein. The knockdown of p0071 in Fmr1− fibroblasts restored stress fibers and an elongated cell shape, thus rescuing the Fmr1− phenotype, whereas overexpression of p0071 in Fmr1+ cells mimicked the Fmr1− phenotype. Moreover, p0071 and FMRP regulated neurite outgrowth and branching in a diametrically opposed way in agreement with the negative regulation of p0071 by FMRP. These results identify p0071 as an important and novel FMRP target and strongly suggest that impaired actin cytoskeletal functions mediated by an excess of p0071 are key aspects underlying the fragile X syndrome.

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“…In vitroexperiments with C-terminal fragments of human Cobl suggested that Cobl may additionally increase the number of barbed ends by severing filaments (Husson et al, 2011). Cobl induced F-actinrich membrane ruffles in COS-7 cells and excessive dendrite formation and branching in neurons and knock-down studies demonstrated that Cobl is critical for dendritogenesis of dissociated hippocampal neurons and of cerebellar Purkinje cells (Ahuja et al, 2007;Haag et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Ciliated sensory hair cell formation and function require the F-BAR protein syndapin I and the WH2 domain-based actin nucleator Cobl

Schüler

Hauptmann

Perner

et al. 2013

Journal of Cell Science

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There was an error published in J. Cell Sci. 126,[196][197][198][199][200][201][202][203][204][205][206][207][208] The sequence of MO sdpI_e3i3 was reported incorrectly in the Materials and Methods section. The correct sequence of the MO sdpI_e3i3 used for this study is gtcaaaatccttcctcacCTCTCTC.We apologise for this mistake. Summary During development, general body plan information must be translated into distinct morphologies of individual cells. Shaping cells is thought to involve cortical cytoskeletal components and Bin-Amphiphysin-Rvs167 (BAR) superfamily proteins. We therefore conducted comprehensive side-by-side loss-of-function studies of zebrafish orthologs of the F-BAR protein syndapin I and the actin nucleator Cobl. Zebrafish syndapin I associates with Cobl. The loss-of-function phenotypes of these proteins were remarkably similar and suggested a common function. Both cobl-and syndapin I-morphant fish showed severe swimming and balance-keeping defects, reflecting an impaired organization and function of the lateral line organ. Their lateral line organs lacked several neuromasts and showed an impaired functionality of the sensory hair cells within the neuromasts. Scanning electron microscopy revealed that sensory hair cells of both cobl-and syndapin I-morphant animals showed defects in the formation of both microtubule-dependent kinocilia and F-actinrich stereocilia. Consistent with the kinocilia defects in sensory hair cells, body length was shortened and the development of body laterality, a process depending on motile cilia, was also impaired. Interestingly, Cobl and syndapin I both localized to the base of forming cilia. Rescue experiments demonstrated that proper formation of ciliated sensory hair cell rosettes relied on Cobl's syndapin Ibinding Cobl homology domain, the actin-nucleating C-terminus of Cobl and the membrane curvature-inducing F-BAR domain of syndapin I. Our data thus suggest that the formation of distinct types of ciliary structures relies on membrane topology-modulating mechanisms that are based on F-BAR domain functions and on complex formation of syndapin I with the actin nucleator Cobl.

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The Actin Nucleator Cobl Is Crucial for Purkinje Cell Development and Works in Close Conjunction with the F-Actin Binding Protein Abp1

Cited by 47 publications

References 33 publications

Dendrite architecture organized by transcriptional control of the F-actin nucleator Spire

Dendrite architecture organized by transcriptional control of the F-actin nucleator Spire

FMRP regulates actin filament organization via the armadillo protein p0071

Ciliated sensory hair cell formation and function require the F-BAR protein syndapin I and the WH2 domain-based actin nucleator Cobl

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