Nuclear Gems and Cajal (Coiled) Bodies in Fetal Tissues: Nucleolar Distribution of the Spinal Muscular Atrophy Protein, SMN

Young, Philip J.; Le, Thanh Van; Dunckley, Matthew G.; Mân, Nguyen thi; Burghes, Arthur H.M.; Morris, Glenn E.

doi:10.1006/excr.2001.5186

Cited by 135 publications

(118 citation statements)

References 43 publications

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“…As the cells shift from a proliferative to a differentiated state in response to dexamethasone treatment, SMN is progressively recruited to CBs. Unlike the situation in adult tissues or explanted adult neurons (Pena et al 2001;Young et al 2001), differentiated UR61 cells also display an increased number of gems. This abundance of gems allowed us to characterize the ultrastructure of this nuclear inclusion, revealing the existence of a morphologically distinct nuclear body.…”

Section: Introductionmentioning

confidence: 79%

“…Untreated and dexamethasone-treated UR61 cells were transfected for 18 h using FuGene 6 transfection reagent (Roche) according to the manufacturer's instructions. For drug treatments, undifferentiated and differentiated UR61 cells were incubated for 24 h with the vehicle (DMSO) or with the methyltransferase inhibitors 5′-deoxy-5′-methylthioadenosine (MTA, Sigma), at a final concentration of 750 μM (Boisvert et al 2002), or with 100 μM adenosine dialdehyde (AdOx, Sigma), as previously reported (Young et al 2001).…”

Section: Cell Culture Transfection Assays and Treatmentsmentioning

confidence: 99%

“…The composition of CBs can also change during development. Morris and colleagues showed that the survival of motor neurons (SMN) protein complex colocalizes withfactors appear as independent nuclear bodies during embryonic development (Young et al 2001). The colocalization of SMN and coilin progressively increases with fetal age, suggesting that recruitment of SMN to CBs is developmentally regulated (Young et al 2001).…”

Section: Introductionmentioning

confidence: 99%

“…Morris and colleagues showed that the survival of motor neurons (SMN) protein complex colocalizes withfactors appear as independent nuclear bodies during embryonic development (Young et al 2001). The colocalization of SMN and coilin progressively increases with fetal age, suggesting that recruitment of SMN to CBs is developmentally regulated (Young et al 2001). Thus, stagespecific changes in nuclear organization, similar to the well-documented rearrangements of cytoplasmic components, are important, pre-programmed aspects of neuronal differentiation.…”

Section: Introductionmentioning

confidence: 99%

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Targeting SMN to Cajal bodies and nuclear gems during neuritogenesis

et al. 2004

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Neurite outgrowth is a central feature of neuronal differentiation. PC12 cells are a good model system for studying the peripheral nervous system and the outgrowth of neurites. In addition to the dramatic changes observed in the cytoplasm, neuronal differentiation is also accompanied by striking changes in nuclear morphology. The large and sustained increase in nuclear transcription during neuronal differentiation requires synthesis of a large number of factors involved in pre-mRNA processing. We show that the number and composition of the nuclear subdomains called Cajal bodies and gems changes during the course of N-ras-induced neuritogenesis in the PC12-derived cell line UR61. The Cajal bodies found in undifferentiated cells are largely devoid of the survival of motor neurons (SMN) protein product. As cells shift to a differentiated state, SMN is not only globally upregulated, but is progressively recruited to Cajal bodies. Additional SMN foci (also known as Gemini bodies, gems) can also be detected. Using dual-immunogold labeling electron microscopy and mouse embryonic fibroblasts lacking the coilin protein, we show that gems clearly represent a distinct category of nuclear body.

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Section: Introductionmentioning

confidence: 79%

Section: Cell Culture Transfection Assays and Treatmentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeting SMN to Cajal bodies and nuclear gems during neuritogenesis

et al. 2004

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“…Identification of missense mutations in these regions indicates that each of these domains may be functionally important [79]. The SMN protein is found in the nucleus and cytoplasm of all cells, but most abundantly in α-motoneurons [5,7,91]. Within the nucleus, the SMN protein forms heteromeric complexes and seems to play an important role in small ribonucleoproteins (snRNPs) biogenesis (such as hnRNP U protein and the small RNA binding protein) and pre-mRNA processing (splicing) [26,96].…”

Section: Smn Protein and Its Functionsmentioning

confidence: 99%

Pathogenesis of proximal autosomal recessive spinal muscular atrophy

Šimić

2008

Acta Neuropathol

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Although it is known that deletions or mutations of the SMN1 gene on chromosome 5 cause decreased levels of the SMN protein in subjects with proximal autosomal recessive spinal muscular atrophy (SMA), the exact sequence of pathological events leading to selective motoneuron cell death is not fully understood yet. In this review, new findings regarding the dual cellular role of the SMN protein (translocation of β-actin to axonal growth cones and snRNP biogenesis/pre-mRNA splicing) were integrated with recent data obtained by detailed neuropathological examination of SMA and control subjects. A presumptive series of 10 pathogenetic events for SMA is proposed as follows: (1) deletions or mutations of the SMN1 gene, (2) increased SMN mRNA decay and reduction in full-length functional SMN protein, (3) impaired motoneuron axonoand dendrogenesis, (4) failure of motoneurons to form synapses with corticospinal fibers from upper motoneurons, (5) abnormal motoneuron migration towards ventral spinal roots, (6) inappropriate persistence of motoneuron apoptosis due to impaired differentiation and motoneuron displacement, (7) substantial numbers of motoneurons continuing to migrate abnormally ("heterotopic motoneurons") and entering into the ventral roots, (8) attracted glial cells following these heterotopic motoneurons, which form the glial bundles of ventral roots, (9) impaired axonal transport of actin, causing remaining motoneurons to become chromatolytic, and (10) eventual death of all apoptotic, heterotopic and chromatolytic neurons, with apoptosis being more rapid and predominating in the earlier stages, with death of heterotopic and chromatolytic neurons occurring more slowly by necrosis during the later stages of SMA. According to this model, the motoneuron axonopathy is more important for pathogenesis than the ubiquitous nuclear splicing deficit. It is also supposed that individually variable levels of SMN protein, together with influences of other phenotype modifier genes and their products, cause the clinical SMA spectrum through differential degree of motoneuron functional loss.

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SMN and Gemins: ‘We are family’ … or are we?

Cauchi¹

2010

BioEssays

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Gemins 2-8 and Unr-interacting protein (UNRIP) are intimate partners of the survival motor neuron (SMN) protein, which is the determining factor for the neuromuscular disorder spinal muscular atrophy (SMA). The most documented role of SMN, Gemins and UNRIP occurs within the large macromolecular SMN complex and involves the cytoplasmic assembly of spliceosomal uridine-rich small nuclear ribonucleoproteins (UsnRNPs), a housekeeping process critical in all cells. Several reports detailing alternative functions for SMN in either motor neurons or skeletal muscles may, however, hold the answer to the extreme neuromuscular tissue specificity observed in SMA. Recent discoveries indicate that collaboration between SMN and Gemins also extends to these non-canonical functions, hence raising the possibility that mutations in Gemin genes may be the cause of unlinked neuromuscular hereditary syndromes. This review evaluates the functions of Gemins and UNRIP inside the SMN complex and discusses whether these less notorious SMN complex members are capable of acting independently of SMN.

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Nuclear Gems and Cajal (Coiled) Bodies in Fetal Tissues: Nucleolar Distribution of the Spinal Muscular Atrophy Protein, SMN

Cited by 135 publications

References 43 publications

Targeting SMN to Cajal bodies and nuclear gems during neuritogenesis

Targeting SMN to Cajal bodies and nuclear gems during neuritogenesis

Pathogenesis of proximal autosomal recessive spinal muscular atrophy

SMN and Gemins: ‘We are family’ … or are we?

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