The survival motor neurons protein uses its ZPR for nuclear localization

2001 ◽  
Vol 3 (4) ◽  
pp. E93-E94 ◽  
Author(s):  
A. Gregory Matera ◽  
Michael D. Hebert
Keyword(s):  
Nuclear Localization ◽  
Motor Neurons ◽  
Survival Motor Neurons

scholarly journals Triptolide increases transcript and protein levels of survival motor neurons in human SMA fibroblasts and improves survival in SMA-like mice

2012 ◽  
Vol 166 (3) ◽  
pp. 1114-1126 ◽  
Author(s):  
Ya-Yun Hsu ◽  
Yuh-Jyh Jong ◽  
Hsin-Hung Tsai ◽  
Yu-Ting Tseng ◽  
Li-Mei An ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Survival Motor Neurons ◽  
Protein Levels

scholarly journals Dephosphorylation of survival motor neurons (SMN) by PPM1G/PP2Cγ governs Cajal body localization and stability of the SMN complex

2007 ◽  
Vol 179 (3) ◽  
pp. 451-465 ◽  
Author(s):  
Sebastian Petri ◽  
Matthias Grimmler ◽  
Sabine Over ◽  
Utz Fischer ◽  
Oliver J. Gruss
Keyword(s):  
Motor Neurons ◽  
Survival Motor Neuron ◽  
Cajal Body ◽  
Sm Proteins ◽  
Interacting Protein ◽  
Survival Motor Neurons ◽  
Small Nuclear Ribonucleoprotein ◽  
Smn Complex ◽  
Catalytically Active ◽  
And Function

The survival motor neuron (SMN) complex functions in maturation of uridine-rich small nuclear ribonucleoprotein (RNP) particles. SMN mediates the cytoplasmic assembly of Sm proteins onto uridine-rich small RNAs, and then participates in targeting RNPs to nuclear Cajal bodies (CBs). Recent studies have suggested that phosphorylation might control localization and function of the SMN complex. Here, we show that the nuclear phosphatase PPM1G/PP2Cγ interacts with and dephosphorylates the SMN complex. Small interfering RNA knockdown of PPM1G leads to an altered phosphorylation pattern of SMN and Gemin3, loss of SMN from CBs, and reduced stability of SMN. Accumulation in CBs is restored upon overexpression of catalytically active, but not that of inactive, PPM1G. This demonstrates that PPM1G's phosphatase activity is necessary to maintain SMN subcellular distribution. Concomitant knockdown of unr interacting protein (unrip), a component implicated in cytoplasmic retention of the SMN complex, also rescues the localization defects. Our data suggest that an interplay between PPM1G and unrip determine compartment-specific phosphorylation patterns, localization, and function of the SMN complex.

scholarly journals A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle

2007 ◽  
Vol 176 (6) ◽  
pp. 831-841 ◽  
Author(s):  
T.K. Rajendra ◽  
Graydon B. Gonsalvez ◽  
Michael P. Walker ◽  
Karl B. Shpargel ◽  
Helen K. Salz ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Spinal Muscular Atrophy ◽  
Motor Neurons ◽  
Striated Muscle ◽  
Flight Muscle ◽  
Muscular Atrophy ◽  
Survival Motor Neurons ◽  
Protein Levels

Mutations in human survival motor neurons 1 (SMN1) cause spinal muscular atrophy (SMA) and are associated with defects in assembly of small nuclear ribonucleoproteins (snRNPs) in vitro. However, the etiological link between snRNPs and SMA is unclear. We have developed a Drosophila melanogaster system to model SMA in vivo. Larval-lethal Smn-null mutations show no detectable snRNP reduction, making it unlikely that these animals die from global snRNP deprivation. Hypomorphic mutations in Smn reduce dSMN protein levels in the adult thorax, causing flightlessness and acute muscular atrophy. Mutant flight muscle motoneurons display pronounced axon routing and arborization defects. Moreover, Smn mutant myofibers fail to form thin filaments and phenocopy null mutations in Act88F, which is the flight muscle–specific actin isoform. In wild-type muscles, dSMN colocalizes with sarcomeric actin and forms a complex with α-actinin, the thin filament crosslinker. The sarcomeric localization of Smn is conserved in mouse myofibrils. These observations suggest a muscle-specific function for SMN and underline the importance of this tissue in modulating SMA severity.

scholarly journals The nuclear ubiquitin ligase adaptor SPOP is a conserved regulator of C9orf72 dipeptide toxicity

2021 ◽  
Vol 118 (40) ◽  
pp. e2104664118
Author(s):  
Carley Snoznik ◽  
Valentina Medvedeva ◽  
Jelena Mojsilovic-Petrovic ◽  
Paige Rudich ◽  
James Oosten ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Motor Neurons ◽  
Ubiquitin Ligase ◽  
Multiple Cancer ◽  
Cancer Subtypes ◽  
Nuclear Localization Signals ◽  
C Elegans ◽  
Hexanucleotide Repeat ◽  
Genome Wide ◽  
Bromodomain Proteins

A hexanucleotide repeat expansion in the C9orf72 gene is the most common cause of inherited amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Unconventional translation of the C9orf72 repeat produces dipeptide repeat proteins (DPRs). Previously, we showed that the DPRs PR50 and GR50 are highly toxic when expressed in Caenorhabditis elegans, and this toxicity depends on nuclear localization of the DPR. In an unbiased genome-wide RNA interference (RNAi) screen for suppressors of PR50 toxicity, we identified 12 genes that consistently suppressed either the developmental arrest and/or paralysis phenotype evoked by PR50 expression. All of these genes have vertebrate homologs, and 7 of 12 contain predicted nuclear localization signals. One of these genes was spop-1, the C. elegans homolog of SPOP, a nuclear localized E3 ubiquitin ligase adaptor only found in metazoans. SPOP is also required for GR50 toxicity and functions in a genetic pathway that includes cul-3, which is the canonical E3 ligase partner for SPOP. Genetic or pharmacological inhibition of SPOP in mammalian primary spinal cord motor neurons suppressed DPR toxicity without affecting DPR expression levels. Finally, we find that knockdown of bromodomain proteins in both C. elegans and mammalian neurons, which are known SPOP ubiquitination targets, suppresses the protective effect of SPOP inhibition. Together, these data suggest a model in which SPOP promotes the DPR-dependent ubiquitination and degradation of BRD proteins. We speculate the pharmacological manipulation of this pathway, which is currently underway for multiple cancer subtypes, could also represent an entry point for therapeutic intervention to treat C9orf72 FTD/ALS.

scholarly journals ZPR1 Is Essential for Survival and Is Required for Localization of the Survival Motor Neurons (SMN) Protein to Cajal Bodies

2005 ◽  
Vol 25 (7) ◽  
pp. 2744-2756 ◽  
Author(s):  
Laxman Gangwani ◽  
Richard A. Flavell ◽  
Roger J. Davis
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Zinc Finger Protein ◽  
Muscular Atrophy ◽  
Cajal Bodies ◽  
Survival Motor Neurons ◽  
Small Nuclear Ribonucleoprotein ◽  
Smn Protein ◽  
Axonal Defects ◽  
Interfering Rna

ABSTRACT Mutation of the survival motor neurons 1 (SMN1) gene causes motor neuron apoptosis and represents the major cause of spinal muscular atrophy in humans. Biochemical studies have established that the SMN protein plays an important role in spliceosomal small nuclear ribonucleoprotein (snRNP) biogenesis and that the SMN complex can interact with the zinc finger protein ZPR1. Here we report that targeted ablation of the Zpr1 gene in mice disrupts the subcellular localization of both SMN and spliceosomal snRNPs. Specifically, SMN localization to Cajal bodies and gems was not observed in cells derived from Zpr1−/− embryos and the amount of cytoplasmic snRNP detected in Zpr1 −/− embryos was reduced compared with that in wild-type embryos. We found that Zpr1 −/− mice die during early embryonic development, with reduced proliferation and increased apoptosis. These effects of Zpr1 gene disruption were confirmed and extended in studies of cultured motor neuron-like cells using small interfering RNA-mediated Zpr1 gene suppression; ZPR1 deficiency caused growth cone retraction, axonal defects, and apoptosis. Together, these data indicate that ZPR1 contributes to the regulation of SMN complexes and that it is essential for cell survival.

scholarly journals Self-association of Coilin Reveals a Common Theme in Nuclear Body Localization

2000 ◽  
Vol 11 (12) ◽  
pp. 4159-4171 ◽  
Author(s):  
Michael D. Hebert ◽  
A. Gregory Matera
Keyword(s):  
Motor Neurons ◽  
Nuclear Body ◽  
Nuclear Bodies ◽  
Interaction Domain ◽  
Interacting Protein ◽  
Survival Motor Neurons ◽  
Marker Proteins ◽  
Localization Signal ◽  
Self Association ◽  
Necessary And Sufficient

We have found that coilin, the marker protein for Cajal bodies (coiled bodies, CBs), is a self-interacting protein, and we have mapped the domain responsible for this activity to the amino-terminus. Together with a nuclear localization signal, the self-interaction domain is necessary and sufficient for localization to CBs. Overexpression of various wild-type and mutant coilin constructs in HeLa cells results in disruption of both CBs and survival motor neurons (SMN) gems. Additionally, we have identified a cryptic nucleolar localization signal (NoLS), within the coilin protein, which may be exposed in specific coilin phospho-isoforms. The implications of these findings are discussed in light of the fact that other proteins known to localize within nuclear bodies (e.g., PML, SMN and Sam68) can also self-associate. Thus protein self-interaction appears to be a general feature of nuclear body marker proteins.

Androgen-induced plasticity at a “vocal” neuromuscular synapse

1994 ◽  
Vol 52 ◽  
pp. 32-33
Author(s):  
Darcy B. Kelley ◽  
Martha L. Tobias ◽  
Mark Ellisman
Keyword(s):  
Xenopus Laevis ◽  
Motor Neurons ◽  
Sexual Differentiation ◽  
Molecular Basis ◽  
Neuromuscular Synapse ◽  
Sexually Dimorphic ◽  
Intracellular Protein ◽  
Developmental Program ◽  
Androgen Action ◽  
Clawed Frog

Brain and muscle are sexually differentiated tissues in which masculinization is controlled by the secretion of androgens from the testes. Sensitivity to androgen is conferred by the expression of an intracellular protein, the androgen receptor. A central problem of sexual differentiation is thus to understand the cellular and molecular basis of androgen action. We do not understand how hormone occupancy of a receptor translates into an alteration in the developmental program of the target cell. Our studies on sexual differentiation of brain and muscle in Xenopus laevis are designed to explore the molecular basis of androgen induced sexual differentiation by examining how this hormone controls the masculinization of brain and muscle targets.Our approach to this problem has focused on a highly androgen sensitive, sexually dimorphic neuromuscular system: laryngeal muscles and motor neurons of the clawed frog, Xenopus laevis. We have been studying sex differences at a synapse, the laryngeal neuromuscular junction, which mediates sexually dimorphic vocal behavior in Xenopus laevis frogs.

386: Nuclear Localization of ERBB3: A Potential Diagnostic/Prognostic Marker of Prostate Cancer

2005 ◽  
Vol 173 (4S) ◽  
pp. 105-106
Author(s):  
Ismaël H. Koumakpayi ◽  
Jean-Simon Diallo ◽  
Cecile Le Page ◽  
Laurent Lessard ◽  
Martin E. Gleave ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Marker ◽  
Nuclear Localization
Sign in / Sign up

Export Citation Format

Share Document