Mammalian STE20-like kinase 2, not kinase 1, mediates photoreceptor cell death during retinal detachment

H. Matsumoto, Y. Murakami, K. Kataoka, H. Lin, K. M. Connor, J. W. Miller, D. Zhou, J. Avruch, D. G. Vavvas

Research output: Contribution to journalArticle

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Abstract

Photoreceptor cell death is the definitive cause of vision loss in retinal detachment (RD). Mammalian STE20-like kinase (MST) is a master regulator of both cell death and proliferation and a critical factor in development and tumorigenesis. However, to date the role of MST in neurodegeneration has not been fully explored. Utilizing MST1-/- and MST2-/- mice we identified MST2, but not MST1, as a regulator of photoreceptor cell death in a mouse model of RD. MST2-/- mice demonstrated significantly decreased photoreceptor cell death and outer nuclear layer (ONL) thinning after RD. Additionally, caspase-3 activation was attenuated in MST2-/- mice compared to control mice after RD. The transcription of p53 upregulated modulator of apoptosis (PUMA) and Fas was also reduced in MST2-/- mice post-RD. Retinas of MST2-/- mice displayed suppressed nuclear relocalization of phosphorylated YAP after RD. Consistent with the reduction of photoreceptor cell death, MST2-/- mice showed decreased levels of proinflammatory cytokines such as monocyte chemoattractant protein 1 and interleukin 6 as well as attenuated inflammatory CD11b cell infiltration during the early phase of RD. These results identify MST2, not MST1, as a critical regulator of caspase-mediated photoreceptor cell death in the detached retina and indicate its potential as a future neuroprotection target.

Original languageEnglish
Article numbere1269
JournalCell Death and Disease
Volume5
DOIs
Publication statusPublished - May 29 2014

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Photoreceptor Cells
Retinal Detachment
Cell Death
Phosphotransferases
Retina
Chemokine CCL2
Caspases
Caspase 3
Interleukin-6
Carcinogenesis
Cell Proliferation
Apoptosis
Cytokines

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

Mammalian STE20-like kinase 2, not kinase 1, mediates photoreceptor cell death during retinal detachment. / Matsumoto, H.; Murakami, Y.; Kataoka, K.; Lin, H.; Connor, K. M.; Miller, J. W.; Zhou, D.; Avruch, J.; Vavvas, D. G.

In: Cell Death and Disease, Vol. 5, e1269, 29.05.2014.

Research output: Contribution to journalArticle

Matsumoto, H. ; Murakami, Y. ; Kataoka, K. ; Lin, H. ; Connor, K. M. ; Miller, J. W. ; Zhou, D. ; Avruch, J. ; Vavvas, D. G. / Mammalian STE20-like kinase 2, not kinase 1, mediates photoreceptor cell death during retinal detachment. In: Cell Death and Disease. 2014 ; Vol. 5.
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abstract = "Photoreceptor cell death is the definitive cause of vision loss in retinal detachment (RD). Mammalian STE20-like kinase (MST) is a master regulator of both cell death and proliferation and a critical factor in development and tumorigenesis. However, to date the role of MST in neurodegeneration has not been fully explored. Utilizing MST1-/- and MST2-/- mice we identified MST2, but not MST1, as a regulator of photoreceptor cell death in a mouse model of RD. MST2-/- mice demonstrated significantly decreased photoreceptor cell death and outer nuclear layer (ONL) thinning after RD. Additionally, caspase-3 activation was attenuated in MST2-/- mice compared to control mice after RD. The transcription of p53 upregulated modulator of apoptosis (PUMA) and Fas was also reduced in MST2-/- mice post-RD. Retinas of MST2-/- mice displayed suppressed nuclear relocalization of phosphorylated YAP after RD. Consistent with the reduction of photoreceptor cell death, MST2-/- mice showed decreased levels of proinflammatory cytokines such as monocyte chemoattractant protein 1 and interleukin 6 as well as attenuated inflammatory CD11b cell infiltration during the early phase of RD. These results identify MST2, not MST1, as a critical regulator of caspase-mediated photoreceptor cell death in the detached retina and indicate its potential as a future neuroprotection target.",
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