CIB1 protects against MPTP-induced neurotoxicity through inhibiting ASK1

Kyoung Wan Yoon; Hyun Suk Yang; Young Mok Kim; Yeonsil Kim; Seongman Kang; Woong Sun; Ulhas P. Naik; Leslie V. Parise; Eui Ju Choi

doi:10.1038/s41598-017-12379-3

CIB1 protects against MPTP-induced neurotoxicity through inhibiting ASK1

Kyoung Wan Yoon, Hyun Suk Yang, Young Mok Kim, Yeonsil Kim, Seongman Kang, Woong Sun, Ulhas P. Naik, Leslie V. Parise, Eui Ju Choi

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Abstract

Calcium and integrin binding protein 1 (CIB1) is a calcium-binding protein that was initially identified as a binding partner of platelet integrin α_IIb. Although CIB1 has been shown to interact with multiple proteins, its biological function in the brain remains unclear. Here, we show that CIB1 negatively regulates degeneration of dopaminergic neurons in a mouse model of Parkinson's disease using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Genetic deficiency of the CIB1 gene enhances MPTP-induced neurotoxicity in dopaminergic neurons in CIB1^-/- mice. Furthermore, RNAi-mediated depletion of CIB1 in primary dopaminergic neurons potentiated 1-methyl-4-phenyl pyrinidium (MPP⁺)-induced neuronal death. CIB1 physically associated with apoptosis signal-regulating kinase 1 (ASK1) and thereby inhibited the MPP⁺-induced stimulation of the ASK1-mediated signaling cascade. These findings suggest that CIB1 plays a protective role in MPTP/MPP⁺-induced neurotoxicity by blocking ASK1-mediated signaling.

Original language	English
Article number	12178
Journal	Scientific reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-12379-3
Publication status	Published - 2017 Dec 1

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title = "CIB1 protects against MPTP-induced neurotoxicity through inhibiting ASK1",

abstract = "Calcium and integrin binding protein 1 (CIB1) is a calcium-binding protein that was initially identified as a binding partner of platelet integrin αIIb. Although CIB1 has been shown to interact with multiple proteins, its biological function in the brain remains unclear. Here, we show that CIB1 negatively regulates degeneration of dopaminergic neurons in a mouse model of Parkinson's disease using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Genetic deficiency of the CIB1 gene enhances MPTP-induced neurotoxicity in dopaminergic neurons in CIB1-/- mice. Furthermore, RNAi-mediated depletion of CIB1 in primary dopaminergic neurons potentiated 1-methyl-4-phenyl pyrinidium (MPP+)-induced neuronal death. CIB1 physically associated with apoptosis signal-regulating kinase 1 (ASK1) and thereby inhibited the MPP+-induced stimulation of the ASK1-mediated signaling cascade. These findings suggest that CIB1 plays a protective role in MPTP/MPP+-induced neurotoxicity by blocking ASK1-mediated signaling.",

author = "Yoon, {Kyoung Wan} and Yang, {Hyun Suk} and Kim, {Young Mok} and Yeonsil Kim and Seongman Kang and Woong Sun and Naik, {Ulhas P.} and Parise, {Leslie V.} and Choi, {Eui Ju}",

note = "Funding Information: This work was supported by the National Research Foundation grant (NRF-2017R1A2B2008193) and by the BRL grant (NRF-2015R1A4A1041919) funded by the Ministry of Science, ICT & Future Planning of Korea, and by a Korea University grant (E.-J.C.). Publisher Copyright: {\textcopyright} 2017 The Author(s).",

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doi = "10.1038/s41598-017-12379-3",

language = "English",

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T1 - CIB1 protects against MPTP-induced neurotoxicity through inhibiting ASK1

AU - Yoon, Kyoung Wan

AU - Yang, Hyun Suk

AU - Kim, Young Mok

AU - Kim, Yeonsil

AU - Kang, Seongman

AU - Sun, Woong

AU - Naik, Ulhas P.

AU - Parise, Leslie V.

AU - Choi, Eui Ju

N1 - Funding Information: This work was supported by the National Research Foundation grant (NRF-2017R1A2B2008193) and by the BRL grant (NRF-2015R1A4A1041919) funded by the Ministry of Science, ICT & Future Planning of Korea, and by a Korea University grant (E.-J.C.). Publisher Copyright: © 2017 The Author(s).

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Calcium and integrin binding protein 1 (CIB1) is a calcium-binding protein that was initially identified as a binding partner of platelet integrin αIIb. Although CIB1 has been shown to interact with multiple proteins, its biological function in the brain remains unclear. Here, we show that CIB1 negatively regulates degeneration of dopaminergic neurons in a mouse model of Parkinson's disease using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Genetic deficiency of the CIB1 gene enhances MPTP-induced neurotoxicity in dopaminergic neurons in CIB1-/- mice. Furthermore, RNAi-mediated depletion of CIB1 in primary dopaminergic neurons potentiated 1-methyl-4-phenyl pyrinidium (MPP+)-induced neuronal death. CIB1 physically associated with apoptosis signal-regulating kinase 1 (ASK1) and thereby inhibited the MPP+-induced stimulation of the ASK1-mediated signaling cascade. These findings suggest that CIB1 plays a protective role in MPTP/MPP+-induced neurotoxicity by blocking ASK1-mediated signaling.

AB - Calcium and integrin binding protein 1 (CIB1) is a calcium-binding protein that was initially identified as a binding partner of platelet integrin αIIb. Although CIB1 has been shown to interact with multiple proteins, its biological function in the brain remains unclear. Here, we show that CIB1 negatively regulates degeneration of dopaminergic neurons in a mouse model of Parkinson's disease using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Genetic deficiency of the CIB1 gene enhances MPTP-induced neurotoxicity in dopaminergic neurons in CIB1-/- mice. Furthermore, RNAi-mediated depletion of CIB1 in primary dopaminergic neurons potentiated 1-methyl-4-phenyl pyrinidium (MPP+)-induced neuronal death. CIB1 physically associated with apoptosis signal-regulating kinase 1 (ASK1) and thereby inhibited the MPP+-induced stimulation of the ASK1-mediated signaling cascade. These findings suggest that CIB1 plays a protective role in MPTP/MPP+-induced neurotoxicity by blocking ASK1-mediated signaling.

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CIB1 protects against MPTP-induced neurotoxicity through inhibiting ASK1

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