Neural stem cell self‐renewal requires the Mrj co‐chaperone

Watson, Erica D.; Mattar, Pierre; Schuurmans, Carol; Cross, James C.

doi:10.1002/dvdy.22088

Cited by 26 publications

(16 citation statements)

References 52 publications

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“…Interestingly, the co-chaperone Mrj, a mammalian member of the type II group of HSP40 (also known as DnaJB6), has been found to be necessary for self-renewal of neural stem cells (Watson et al, 2009). It is intriguing to speculate that a conserved type II HSP40 co-chaperone-mediated activity may exist for the control of self-renewal and proliferation of stem cells in diverse organisms.…”

Section: Hsp40/dnaj Genesmentioning

confidence: 99%

Stem cell protection mechanisms in planarians: the role of some heat shock genes

Isolani¹,

Conte²,

Deri³

et al. 2012

Int. J. Dev. Biol.

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Planarians contain a large population of stem cells, named neoblasts, and use these for continuous turnover of all cell types. In addition, thanks to the amazing flexibility of these cells, planarians respond well to the effects of stressful situations, for example activating regeneration after trauma. How neoblasts respond to stress and support continuous proliferation, maintaining long-term stability, is still an open question. Heat shock proteins (HSPs) are a complex protein family with key roles in maintaining protein homeostasis, as well as in apoptosis and growthrelated processes. We recently characterized some planarian homologs of hsp genes that are highly expressed in mammalian stem cells, and observed that some of them are critical for neoblast survival/maintenance. The results of these studies support the notion that some HSPs play crucial roles in the modulation of pathways regulating stem cell activity, regeneration and tissue repair. In this review we compare the evidence available for planarian hsp genes and focus on questions emerging from these results.

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Section: Hsp40/dnaj Genesmentioning

confidence: 99%

Stem cell protection mechanisms in planarians: the role of some heat shock genes

Isolani¹,

Conte²,

Deri³

et al. 2012

Int. J. Dev. Biol.

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“…This function was dependent on a functional J domain and required an interaction between DNAJB6, HSPA8 and GSK3β (glycogen synthase kinase 3 beta) [53]. Interestingly DNAJB6 is also highly expressed in the nervous system and is required for the maintenance of neural stem cells [130,131]. Mutations in DNAJB6 have been linked to such diseases as autosomal dominant limb-girdle muscular dystrophy (LGMD), a rare condition characterised by muscle atrophy.…”

Section: Hsp40s As Drug Targets In Cancer and Neurodegenerative Diseasesmentioning

confidence: 98%

Hsp40 Co-chaperones as Drug Targets: Towards the Development of Specific Inhibitors

Pesce

Blatch

Edkins

2015

Topics in Medicinal Chemistry

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The heat shock protein 40 (Hsp40/DNAJ) family of co-chaperones modulates the activity of the major molecular chaperone heat shock protein 70 (Hsp70) protein group. Hsp40 stimulates the basal ATPase activity of Hsp70 and hence regulates the affinity of Hsp70 for substrate proteins. The number of Hsp40 genes in most organisms is substantially greater than the number of Hsp70 genes. Therefore, different Hsp40 family members may regulate different activities of the same Hsp70. This fact, along with increasing knowledge of the function of Hsp40 in diseases, has led to certain Hsp40 isoforms being considered promising drug targets. Here we review the role of Hsp40 in human disease and recent developments towards the creation of Hsp40-specific inhibitors.

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“…It is thus assumed that Dnajb6 may indirectly regulate the calciumregulated protein phosphatase calcineurin (PP2B) which functions as a regulator of gene expression through NFAT in many tissues. Chaperone protein Dnajb6 is also required for neural stem cell self-renewal (Watson et al 2009). These reports support the notion that acupuncture at the acupoints may modulate the gene expression by regulating the regulators of transcription factors such as Dnajb6.…”

Section: Tablementioning

confidence: 99%

Neuroprotective Changes of Striatal Degeneration-Related Gene Expression by Acupuncture in an MPTP Mouse Model of Parkinsonism: Microarray Analysis

2010

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Acupuncture at acupoints GB34 and LR3 has been reported to inhibit nigrostriatal degeneration in Parkinsonism models, yet the genes related to this preventive effect of acupuncture on the nigrostriatal dopaminergic system remain elusive. This study investigated gene expression profile changes in the striatal region of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism models after acupuncture at the acupoints GB34 and LR3 using a whole transcript genechip microarray (Affymetrix genechip mouse gene 1.0 ST array). It was confirmed that acupuncture at these acupoints could inhibit the decrease of tyrosine hydroxylase and dopamine transporter in the nigrostriatal region of the MPTP model while acupuncture at the non-acupoints could not counteract this decrease. Genechip gene array analysis (fold change cutoff 1.3 and P < 0.05) showed that 12 of the 69 probes up-regulated in MPTP when compared to the control were down-regulated by acupuncture at the acupoints. Of these 12 probes, 11 probes (nine annotated genes) were exclusively down-regulated by acupuncture only at the acupoints; the Gfral gene was excluded because it was commonly down-regulated by acupuncture at both the acupoints and the non-acupoints. In addition, 28 of the 189 probes down-regulated in MPTP when compared to the control were up-regulated by acupuncture at the acupoints. Of these 28 probes, 19 probes (seven annotated genes) were exclusively up-regulated by acupuncture only at the acupoints while nine probes were commonly up-regulated by acupuncture at both the acupoints and the non-acupoints. The regulation patterns of representative genes in real-time RT-PCR correlated with those of the genes in the microarray. These results suggest that the 30 probes (16 annotated genes), which are affected by MPTP and acupuncture only at the acupoints, are responsible for exerting in the striatal regions the inhibitory effect of acupuncture at the acupoints on MPTP-induced striatal degeneration.

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Neural stem cell self‐renewal requires the Mrj co‐chaperone

Cited by 26 publications

References 52 publications

Stem cell protection mechanisms in planarians: the role of some heat shock genes

Stem cell protection mechanisms in planarians: the role of some heat shock genes

Hsp40 Co-chaperones as Drug Targets: Towards the Development of Specific Inhibitors

Neuroprotective Changes of Striatal Degeneration-Related Gene Expression by Acupuncture in an MPTP Mouse Model of Parkinsonism: Microarray Analysis

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