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Hippocalcin Promotes Neuronal Differentiation and Inhibits Astrocytic Differentiation in Neural Stem Cells

Title
Hippocalcin Promotes Neuronal Differentiation and Inhibits Astrocytic Differentiation in Neural Stem Cells
Author
정승준
Keywords
TYROSINE-PHOSPHATASE SHP-1OWTH; PHOSPHOLIPASE D1; CALCIUM SENSOR; CORTICAL NEUROGENESIS; HIPPOCAMPAL-NEURONS; BCL-2 EXPRESSION; PROGENITOR CELLS; H19-7 CELLS; KINASE 1
Issue Date
2017-01
Publisher
CELL PRESS
Citation
STEM CELL REPORTS, v. 8, no. 1, page. 95-111
Abstract
Hippocalcin (HPCA) is a calcium-binding protein that is restricted to nervous tissue and contributes to neuronal activity. Here we report that, in addition to inducing neurogenesis, HPCA inhibits astrocytic differentiation of neural stem cells. It promotes neurogenesis by regulating protein kinase C alpha (PKC alpha) activation by translocating to the membrane and binding to phosphoinositide-dependent protein kinase 1 (PDK1), which induces PKC alpha phosphorylation. We also found that phospholipase D1 (PLD1) is implicated in the HPCA-mediated neurogenesis pathway; this enzyme promotes dephosphorylation of signal transducer and activator of transcription 3 (STAT3 [Y705]), which is necessary for astrocytic differentiation. Moreover, we found that the SH2-domain-containing tyrosine phosphatase 1 (SHP-1) acts upstream of STAT3. Importantly, this SHP-1-dependent STAT3-inhibitory mechanism is closely involved in neurogenesis and suppression of gliogenesis by HPCA. Taken together, these observations suggest that HPCA promotes neuronal differentiation through activation of the PKC alpha/PLD1 cascade followed by activation of SHP-1, which dephosphorylates STAT3(Y705), leading to inhibition of astrocytic differentiation.
URI
https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(16)30271-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2213671116302715%3Fshowall%3Dtruehttps://repository.hanyang.ac.kr/handle/20.500.11754/105853
ISSN
2213-6711
DOI
10.1016/j.stemcr.2016.11.009
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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