Expression of CD47/integrin-associated protein induces death of cultured cerebral cortical neurons
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Updated: Sep 30, 2026
Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
Published on: November 6, 2017
Hisatsugu Koshimizu1, Toshiyuki Araki, Satomi Takai
1Division of Protein Biosynthesis, Institute for Protein Research, Osaka University, Suita, Japan.
Abstract:
The death and survival of neuronal cells are regulated by various signaling pathways during development of the brain and in neuronal diseases. Previously, we demonstrated that the neuronal adhesion molecule brain immunoglobulin-like molecule with tyrosine-based activation motifs/SHP substrate 1 (BIT/SHPS-1) is involved in brain-derived neurotrophic factor (BDNF)-promoted neuronal cell survival. Here, we report the apoptosis-inducing effect of CD47/integrin-associated protein (IAP), the heterophilic binding partner of BIT/SHPS-1, on neuronal cells. We generated a recombinant adenovirus vector expressing a neuronal form of CD47/IAP, and found that the expression of CD47/IAP by infection with CD47/IAP adenovirus induced the death of cultured cerebral cortical neurons. The numbers of TdT-mediated biotin-dUTP nick-end labelling (TUNEL)-positive neurons and of cells displaying apoptotic nuclei increased by expression of CD47/IAP. Neuronal cell death was prevented by the addition of the broad-spectrum caspase inhibitor Z-VAD-fmk. Furthermore, we observed that co-expression of CD47/IAP with BIT/SHPS-1 enhanced neuronal cell death, and that BDNF prevented it. These results suggest that CD47/IAP is involved in a novel pathway which regulates caspase-dependent apoptosis of cultured cerebral cortical neurons. CD47/IAP-induced death of cultured cortical neurons may be regulated by the interaction of CD47/IAP with BIT/SHPS-1 and by BDNF.
Insights
CD47/integrin-associated protein (IAP) induces neuronal cell death via caspase-dependent apoptosis. This process is modulated by brain immunoglobulin-like molecule with tyrosine-based activation motifs/SHP substrate 1 (BIT/SHPS-1) interaction and brain-derived neurotrophic factor (BDNF).
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Neuronal cell death and survival are critical processes regulated by signaling pathways in brain development and disease.
- Brain immunoglobulin-like molecule with tyrosine-based activation motifs/SHP substrate 1 (BIT/SHPS-1) is known to promote neuronal survival, particularly in response to brain-derived neurotrophic factor (BDNF).
Purpose of the Study:
- To investigate the role of CD47/integrin-associated protein (IAP), a binding partner of BIT/SHPS-1, in neuronal cell death.
- To elucidate the signaling pathways involved in CD47/IAP-mediated neuronal apoptosis.
Main Methods:
- Generation of a recombinant adenovirus vector expressing a neuronal form of CD47/IAP.
- Infection of cultured cerebral cortical neurons with the CD47/IAP adenovirus.
- Assessment of neuronal apoptosis using TdT-mediated biotin-dUTP nick-end labelling (TUNEL) assay and analysis of apoptotic nuclei.
- Treatment with the caspase inhibitor Z-VAD-fmk.
- Co-expression of CD47/IAP with BIT/SHPS-1 and treatment with BDNF.
Main Results:
- Expression of CD47/IAP induced significant neuronal cell death in cultured cerebral cortical neurons.
- Increased numbers of TUNEL-positive neurons and cells with apoptotic nuclei were observed upon CD47/IAP expression.
- Neuronal death induced by CD47/IAP was prevented by the caspase inhibitor Z-VAD-fmk, indicating caspase-dependent apoptosis.
- Co-expression of CD47/IAP with BIT/SHPS-1 enhanced neuronal cell death, an effect that was prevented by BDNF.
Conclusions:
- CD47/integrin-associated protein (IAP) plays a role in inducing caspase-dependent apoptosis in cultured cerebral cortical neurons.
- CD47/IAP-mediated neuronal death may involve interaction with BIT/SHPS-1 and regulation by BDNF.
- These findings reveal a novel pathway regulating neuronal apoptosis involving CD47/IAP.
