Growth Cone Localization of the mRNA Encoding the Chromatin Regulator HMGN5 Modulates Neurite Outgrowth

Moretti, Francesca; Rolando, Chiara; Winker, Moritz; Ivánek, Robert; Rodríguez, Javier; Kriegsheim, Alex von; Taylor, Verdon; Bustin, Michael; Pertz, Olivier

doi:10.1128/mcb.00133-15

Cited by 23 publications

(24 citation statements)

References 56 publications

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“…In the mouse neuroblastoma cell line N1E-115, the mRNA encoding HMGN5 localizes to growth cones of both neuron-like cells and of hippocampal neurons, where it has the potential to be translated, and that HMGN5 can be retrogradely transported into the nucleus along neurites. Loss of HMGN5 function induces transcriptional changes and impairs neurite outgrowth, while HMGN5 overexpression induces neurite outgrowth and chromatin decompaction suggesting that this HMGN variant plays a role in facilitating growth cone-to-nucleus signaling during neuronal development [39].…”

Section: Neuronal Developmentmentioning

confidence: 99%

Biological Functions of HMGN Chromosomal Proteins

Nanduri

Furusawa

Bustin

2020

IJMS

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Chromatin plays a key role in regulating gene expression programs necessary for the orderly progress of development and for preventing changes in cell identity that can lead to disease. The high mobility group N (HMGN) is a family of nucleosome binding proteins that preferentially binds to chromatin regulatory sites including enhancers and promoters. HMGN proteins are ubiquitously expressed in all vertebrate cells potentially affecting chromatin function and epigenetic regulation in multiple cell types. Here, we review studies aimed at elucidating the biological function of HMGN proteins, focusing on their possible role in vertebrate development and the etiology of disease. The data indicate that changes in HMGN levels lead to cell type-specific phenotypes, suggesting that HMGN optimize epigenetic processes necessary for maintaining cell identity and for proper execution of specific cellular functions. This manuscript contains tables that can be used as a comprehensive resource for all the English written manuscripts describing research aimed at elucidating the biological function of the HMGN protein family.

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Section: Neuronal Developmentmentioning

confidence: 99%

Biological Functions of HMGN Chromosomal Proteins

Nanduri

Furusawa

Bustin

2020

IJMS

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“…Adult PNS neurons show translation and retrograde transport of the transcription factors Stat3α and PPARγ after axotomy (Ben-Yaakov et al, 2012;Lezana et al, 2016). The chromatininteracting protein HMGN5 is synthesized in hippocampal axons, and the protein product is transported to the nucleus to modulate gene expression (Moretti et al, 2015). Axonal synthesis of ATF4 is stimulated by Aβ1-42 peptide and retrogradely transported ATF4 can stimulate neuronal apoptosis (Box 2) (Baleriola et al, 2014).…”

Section: Axonally Synthesized Proteins Support Axon Growthmentioning

confidence: 99%

Axonal mRNA transport and translation at a glance

Sahoo

Smith

Perrone‐Bizzozero

et al. 2018

Journal of Cell Science

105

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Localization and translation of mRNAs within different subcellular domains provides an important mechanism to spatially and temporally introduce new proteins in polarized cells. Neurons make use of this localized protein synthesis during initial growth, regeneration and functional maintenance of their axons. Although the first evidence for protein synthesis in axons dates back to 1960s, improved methodologies, including the ability to isolate axons to purity, highly sensitive RNA detection methods and imaging approaches, have shed new light on the complexity of the transcriptome of the axon and how it is regulated. Moreover, these efforts are now uncovering new roles for locally synthesized proteins in neurological diseases and injury responses. In this Cell Science at a Glance article and the accompanying poster, we provide an overview of how axonal mRNA transport and translation are regulated, and discuss their emerging links to neurological disorders and neural repair.

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“…Consistently, overexpression of axonally targeted amphoterin mRNA, but not cell body restricted mRNA increases axon outgrowth in cultured sensory neurons (95). Another study suggests that the localization and local translation of transcripts coding for high mobility group nucleosome binding domain 5 (HMGN5) links neurite outgrowth to chromatin regulation in the nucleus (108). The mRNA coding for HMGN5 localizes to growth cones via its 3ЈUTR and the HMGN5 protein can be retrogradely transported to influence chromatin structure in a differentiated neuroblastoma cell line and in cultured hippocampal neurons (108).…”

Section: Figmentioning

confidence: 88%

“…Another study suggests that the localization and local translation of transcripts coding for high mobility group nucleosome binding domain 5 (HMGN5) links neurite outgrowth to chromatin regulation in the nucleus (108). The mRNA coding for HMGN5 localizes to growth cones via its 3ЈUTR and the HMGN5 protein can be retrogradely transported to influence chromatin structure in a differentiated neuroblastoma cell line and in cultured hippocampal neurons (108). Together these studies highlight that proteins typically known for their nuclear function as transcription factors or chromatin regulator also play important roles in axonal signaling, transducing information from distantly located axon to the nucleus to control neuronal development, survival, or repair.…”

Section: Figmentioning

confidence: 99%

Signaling Over Distances

Saito

Cavalli

2016

Molecular & Cellular Proteomics

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Neurons are extremely polarized cells. Axon lengths often exceed the dimension of the neuronal cell body by several orders of magnitude. These extreme axonal lengths imply that neurons have mastered efficient mechanisms for long distance signaling between soma and synaptic terminal. These elaborate mechanisms are required for neuronal development and maintenance of the nervous system. Neurons can fine-tune long distance signaling through calcium wave propagation and bidirectional transport of proteins, vesicles, and mRNAs along microtubules. The signal transmission over extreme lengths also ensures that information about axon injury is communicated to the soma and allows for repair mechanisms to be engaged. This review focuses on the different mechanisms employed by neurons to signal over long axonal distances and how signals are interpreted in the soma, with an emphasis on proteomic studies. We also discuss how proteomic approaches could help further deciphering the signaling mechanisms operating over long distance in axons. Neurons have unique and highly polarized morphologies. The axon allows intracellular communication between the cell soma and the distantly located synaptic terminal. The extreme length of axons relative to the cell soma diameter poses great challenges for neuronal development, maintenance, and repair. Anterograde and retrograde axonal transport of proteins vesicles and RNA along the microtubule tracks in the axon is crucial to sustain the required signaling events underlying development and maintenance of the nervous system. The retrograde transport system is also used following axon injury to communicate information from the site of injury back to the soma. Communication between distant axon locations and the cell soma is also ensured by a more rapid signal encoded in calcium waves. Incoming signals from distant axon locations are interpreted by the soma to regulate gene expression for survival or repair. The neuronal epigenome is also influenced by incoming signals to appropriately coordinate transcriptional responses. In this review, we discuss the state of the field regarding the different mechanisms employed by neurons to signal intracellularly over long distances in axons and how signals are interpreted in the cell soma, with an emphasis on proteomic studies. We also discuss how the use of proteomics could further help in understanding long distance signaling system in axons. The communication employed by neurons to signal along dendrites has been reviewed in detail elsewhere (1) and will not be discussed here.Calcium Influx, Back Propagation, and Long Distance Effects-Alterations in axonal calcium levels affect multiple and diverse signaling events, including local protein synthesis and degradation. These local signals can have long distance effects. Axon injury provides a powerful system to study the role of calcium in axonal signaling, because injury-induced calcium influx in the axon triggers important downstream events at the injury site and the soma (Fig.

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Growth Cone Localization of the mRNA Encoding the Chromatin Regulator HMGN5 Modulates Neurite Outgrowth

Cited by 23 publications

References 56 publications

Biological Functions of HMGN Chromosomal Proteins

Biological Functions of HMGN Chromosomal Proteins

Axonal mRNA transport and translation at a glance

Signaling Over Distances

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