Solution structure and dynamics of mouse ARMET

Hoseki, Jun; Sasakawa, Hiroaki; Yamaguchi, Yoshiki; Maeda, Momoe; Kubota, Hiroshi; Kato, Koichi; Nagata, Kazuhiro

doi:10.1016/j.febslet.2010.03.008

Cited by 22 publications

(17 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, MANF transcripts and protein levels are increased after ischemic and epileptic insults in the cerebral cortex, suggesting that MANF may have neuroprotective effects against neurotoxins and cerebral ischemia (Lindholm et al, 2008;Voutilainen et al, 2009;Yu et al, 2010). The crystal structure of mammalian MANF has revealed that the amino-terminal region of MANF family members contains a saposin-like domain which may interact with lipids and membranes whereas the carboxy-terminal region includes an intradomain cysteine bridge in a CXXC motif which may protect cells from endoplasmic reticulum stress induced apoptosis (Hellman et al, 2010;Hoseki et al, 2010;Parkash et al, 2009). MANF is also found in invertebrates; for instance, Drosophila MANF is expressed in glia and neurons, and knocking out manf expression leads to neuronal degeneration causing embryonic lethality, indicating that MANF is required for the maintenance of neural cells in the fly (Palgi et al, 2009).…”

Section: Introductionmentioning

confidence: 98%

MANF regulates dopaminergic neuron development in larval zebrafish

Chen

Sundvik

Rozov

et al. 2012

Developmental Biology

View full text Add to dashboard Cite

Mesencephalic astrocyte derived neurotrophic factor (MANF) is recognized as a dopaminergic neurotrophic factor, which can protect dopaminergic neurons from neurotoxic damage. However, little is known about the function of MANF during the vertebrate development. Here, we report that MANF expression is widespread during embryonic development and in adult organs analyzed by qPCR and in situ hybridization in zebrafish. Knockdown of MANF expression with antisense splice-blocking morpholino oligonucleotides resulted in no apparent abnormal phenotype. Nevertheless, the dopamine level of MANF morphants was lower than that of the wild type larvae, the expression levels of the two tyrosine hydroxylase gene transcripts were decreased and a decrease in neuron number in certain groups of th1 and th2 cells in the diencephalon region in MANF morphants was observed. These defects were rescued by injection of exogenous manf mRNA. Strikingly, manf mRNA could partly restore the decrease of th1 positive cells in Nr4a2-deficient larvae. These results suggest that MANF is involved in the regulation of the development of dopaminergic system in zebrafish.

show abstract

Section: Introductionmentioning

confidence: 98%

MANF regulates dopaminergic neuron development in larval zebrafish

Chen

Sundvik

Rozov

et al. 2012

Developmental Biology

View full text Add to dashboard Cite

show abstract

“…Human MANF shares 59% amino acid identity with CDNF. The study on MANF solution structure revealed that MANF is composed of two domains, a saposin-like N-terminal domain and a well-conserved flexible C-terminal domain with a cysteine bridge [6,7]. The cysteine bridge may be involved in catalyzing the formation of intramolecular disulfide bonds and protein folding in the endoplasmic reticulum (ER) because of its similarity to the active site motif of thiol/disulfide oxidoreductases [8,9].…”

Section: Introductionmentioning

confidence: 99%

Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation

Shen

Sun

Wang

et al. 2012

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundMesencephalic astrocyte-derived neurotrophic factor (MANF), a 20 kDa secreted protein, was originally derived from a rat mesencephalic type-1 astrocyte cell line. MANF belongs to a novel evolutionally conserved family of neurotrophic factors along with conserved dopamine neurotrophic factor. In recent years, ever-increasing evidence has shown that both of them play a remarkable protective role against various injuries to neurons in vivo or in vitro. However, the characteristics of MANF expression in the different types of glial cells, especially in astrocytes, remain unclear.MethodsThe model of focal cerebral ischemia was induced by rat middle cerebral artery occlusion. Double-labeled immunofluorescent staining was used to identify the types of neural cells expressing MANF. Primarily cultured glial cells were used to detect the response of glial cells to endoplasmic reticulum stress stimulation. Propidium iodide staining was used to determine dead cells. Reverse transcription PCR and western blotting were used to detect the levels of mRNA and proteins.ResultsWe found that MANF was predominantly expressed in neurons in both normal and ischemic cortex. Despite its name, MANF was poorly expressed in glial cells, including astrocytes, in normal brain tissue. However, the expression of MANF was upregulated in the glial cells under focal cerebral ischemia, including the astrocytes. This expression was also induced by several endoplasmic reticulum stress inducers and nutrient deprivation in cultured primary glial cells. The most interesting phenomenon observed in this study was the pattern of MANF expression in the microglia. The expression of MANF was closely associated with the morphology and state of microglia, accompanied by the upregulation of BIP/Grp78.ConclusionsThese results indicate that MANF expression was upregulated in the activated glial cells, which may contribute to the mechanism of ischemia-induced neural injury.

show abstract

“…Remarkably, the C-terminal domain is homologous to the SAP (SAF-A/B, Acinus, and PIAS) domain of Ku70 (C-Ku70), a well known inhibitor of proapoptotic Bax (13). During preparation of this article, Hoseki and co-workers (14) have independently determined the NMR structure of MANF (Protein Data Bank code 2RQY). Although the three-dimensional structure is highly similar to our solution structure with an r.m.s.d.…”

mentioning

confidence: 99%

Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) Has a Unique Mechanism to Rescue Apoptotic Neurons

Hellman

Arumäe

et al. 2011

Journal of Biological Chemistry

124

195

View full text Add to dashboard Cite

Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects neurons and repairs the Parkinson diseaselike symptoms in a rat 6-hydroxydopamine model. We show a three-dimensional solution structure of human MANF that differs drastically from other neurotrophic factors. Remarkably, the C-terminal domain of MANF (C-MANF) is homologous to the SAP domain of Ku70, a well known inhibitor of proapoptotic Bax (Bcl-2-associated X protein). Cellular studies confirm that MANF and C-MANF protect neurons intracellularly as efficiently as Ku70.

show abstract

Solution structure and dynamics of mouse ARMET

Cited by 22 publications

References 24 publications

MANF regulates dopaminergic neuron development in larval zebrafish

MANF regulates dopaminergic neuron development in larval zebrafish

Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation

Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) Has a Unique Mechanism to Rescue Apoptotic Neurons

Contact Info

Product

Resources

About