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Copine1 enhances neuronal differentiation of the hippocampal progenitor HiB5 cells.

ABSTRACT: Copine1 is a ubiquitously expressed protein found in various tissues including the brain, but little is known about the physiological function of this protein. Here, we showed that copine1 is involved in neuronal differentiation. Over-expression of copine1 clearly increased neurite outgrowth and expression of Tuj1, a neuronal marker protein, in HiB5 cells. In addition, endogenous copine1 was transiently increased at the early time during neuronal differentiation of HiB5 cells. When the expression of endogenous copine1 was knocked-down by its specific shRNA, PDGF-mediated neurite outgrowth was clearly decreased in HiB5 cells. Furthermore, over-expression of copine1 increased phosphorylation of Akt and copine1-specific shRNA decreased phosphorylation of Akt during neuronal differentiation of HiB5 cells. Interestingly, the phosphorylation level of PI3K, generally known as an upstream protein of Akt, was not changed by copine1 expression. These results suggest that copine1 enhances neuronal differentiation of HiB5 cells not through the PI3K-Akt pathway, but by using another Akt activated signal pathway.

SUBMITTER: Park N

PROVIDER: S-EPMC3887833 | biostudies-other | 2012 Dec

REPOSITORIES: biostudies-other

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Copine1 enhances neuronal differentiation of the hippocampal progenitor HiB5 cells.

Park Nammi N Yoo Jae Cheal JC Ryu Jiwon J Hong Seong-Geun SG Hwang Eun Mi EM Park Jae-Yong JY

Molecules and cells 20121127 6

Copine1 is a ubiquitously expressed protein found in various tissues including the brain, but little is known about the physiological function of this protein. Here, we showed that copine1 is involved in neuronal differentiation. Over-expression of copine1 clearly increased neurite outgrowth and expression of Tuj1, a neuronal marker protein, in HiB5 cells. In addition, endogenous copine1 was transiently increased at the early time during neuronal differentiation of HiB5 cells. When the expressio ...[more]

PMID: 23263657

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Project description:BackgroundActivin A is a protein that participates principally in reproductive functions. In the adult brain, Activin is neuroprotective, but its role in brain development is still elusive.Methodology/principal findingsWe studied if Activin A influences proliferation, differentiation or survival in rat cerebrocortical neural progenitor cells (NPC). After stimulation of NPC with Activin A, phosphorylation and nuclear translocation of Smad 2/3 were induced. In proliferating NPC, Activin produced a significant decrease in cell area and also a discrete increase in the number of neurons in the presence of the mitogen Fibroblast Growth Factor 2. The percentages of cells incorporating BrdU, or positive for the undifferentiated NPC markers Nestin and Sox2, were unchanged after incubation with Activin. In differentiating conditions, continuous treatment with Activin A significantly increased the number of neurons without affecting astroglial differentiation or causing apoptotic death. In cells cultured by extended periods, Activin treatment produced further increases in the proportion of neurons, excluding premature cell cycle exit. In clonal assays, Activin significantly increased neuronal numbers per colony, supporting an instructive role. Activin-induced neurogenesis was dependent on activation of its receptors, since incubation with the type I receptor inhibitor SB431542 or the ligand-trap Follistatin prevented neuronal differentiation. Interestingly, SB431542 or Follistatin by themselves abolished neurogenesis and increased astrogliogenesis, to a similar extent to that induced by Bone Morphogenetic Protein (BMP)4. Co-incubation of these Activin inhibitors with the BMP antagonist Dorsomorphin restored neuronal and astrocytic differentiation to control levels.ConclusionsOur results show an instructive neuronal effect of Activin A in cortical NPC in vitro, pointing out to a relevant role of this cytokine in the specification of NPC towards a neuronal phenotype.

Dataset Information

Copine1 enhances neuronal differentiation of the hippocampal progenitor HiB5 cells.

Publications

Copine1 enhances neuronal differentiation of the hippocampal progenitor HiB5 cells.

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