The actin nucleation factor JMY is a negative regulator of neuritogenesis

Fırat-Karalar, Elif Nur; Hsiue, Peter P.; Welch, Matthew D.

doi:10.1091/mbc.e11-06-0585

Cited by 41 publications

(38 citation statements)

References 61 publications

(125 reference statements)

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“…Our data are similar to those reported in mice, with high levels of expression in the spleen and testis but lower levels in the lung, liver, kidney, and colon. The only discrepancy was human gastric mucosa, in which we found a higher level of JMY than was reported in the mouse [14]. Most positive tissues also expressed P53, consistent with the notion that JMY augments transcriptional activity [1] and suppresses cellular proliferation.…”

Section: Discussionsupporting

confidence: 81%

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JMY protein, a regulator of P53 and cytoplasmic actin filaments, is expressed in normal and neoplastic tissues

et al. 2014

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JMY is a p300-binding protein with dual action: by enhancing P53 transcription in the nucleus, it plays an important role in the cellular response to DNA damage, while by promoting actin filament assembly in the cytoplasm; it induces cell motility in vitro. Therefore, it has been argued that, depending of the cellular setting, it might act either as tumor suppressor or as oncogene. In order to further determine its relevance to human cancer, we produced the monoclonal antibody HMY 117 against a synthetic peptide from the N-terminus region and characterized it on two JMY positive cell lines, MCF7 and HeLa, wild type and after transfection with siRNA to switch off JMY expression. JMY was expressed in normal tissues and heterogeneously in different tumor types, with close correlation between cytoplasmic and nuclear expression. Most noticeable was the loss of expression in some infiltrating carcinomas compared to normal tissue and in in situ carcinomas of the breast, which is consistent with a putative suppressor role. However, as in lymph node metastases, expression of JMY was higher than in primary colorectal and head and neck carcinomas, it might also have oncogenic properties depending on the cellular context by increasing motility and metastatic potential.

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Section: Discussionsupporting

confidence: 81%

“…By Western blotting, widespread expression in normal tissues has been reported in mice and in a small series of mammalian cell lines [14]. We raised and characterized a monoclonal antibody that detects JMY by Western blotting and in formalin-fixed paraffinembedded tissue.…”

Section: Discussionmentioning

confidence: 99%

JMY protein, a regulator of P53 and cytoplasmic actin filaments, is expressed in normal and neoplastic tissues

et al. 2014

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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: 96%

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

Ferreira

et al. 2014

Journal of Cell Science

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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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“…Zuchero et al [12] and Firat-Karalar et al [26] demonstrated that purified JMY biochemically activates Arp2/3 ( Figure 5) induced actin polymerization in a dose dependent fashion. JMY does not induce elongation of preformed filaments but is able to nucleate new filaments, make them to elongate faster and cut filaments to make barbed ends.…”

Section: Jmy and Cell Motilitymentioning

confidence: 92%

“…The role played by JMY in actin regulation does not affect only the motility of the cell but, in the case of the neurons, it is also involved in the development of these cells as JMY inhibits the formation of neurites [26]. This inhibiting activity appears to be due to its function as an actin-assembly protein [26].…”

Section: Jmy and Cell Motilitymentioning

confidence: 99%

The Role of JMY in p53 Regulation.

Adighibe¹

2018

Preprint

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Abstract:Following the event of DNA damage the levels of tumour suppressor protein p53 increases inducing either cell cycle arrest or apoptosis. Junctional Mediating and Regulating Y protein (JMY) is a transcription co-factor involved in p53 regulation. Hence in the event of DNA damage, JMY levels are also upregulated in the nucleus where JMY forms a complex with p300/CREB-binding protein (p300/CBP), Apoptosis-stimulating protein of p53 (ASPP) and Stress responsive activator of p53 (Strap). This co-activator complex then binds to and increases the ability of p53 to induce transcription of proteins triggering apoptosis but not cell cycle arrest. This then suggests that the increase of JMY levels due to DNA damage putatively "direct" p53 activity toward triggering apoptosis. JMY expression is also linked to increased cell motility as it: downregulates the expression of adhesion molecules of the Cadherin family and induces actin nucleation; making cells less adhesive and more mobile, favouring metastasis.All these characteristics taken together imply that JMY therefore possesses both tumour suppressive and tumour promoting capabilities.

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The actin nucleation factor JMY is a negative regulator of neuritogenesis

Abstract: JMY is a p53 cofactor that was recently shown to nucleate actin assembly. Evidence is presented that the function of JMY in actin nucleation is regulated by an inhibitory activity in cells and that JMY has a previously unrecognized function as a modulator of neuritogenesis.

Cited by 41 publications

References 61 publications

JMY protein, a regulator of P53 and cytoplasmic actin filaments, is expressed in normal and neoplastic tissues

JMY protein, a regulator of P53 and cytoplasmic actin filaments, is expressed in normal and neoplastic tissues

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

The Role of JMY in p53 Regulation.

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