Ndr kinases regulate retinal interneuron proliferation and homeostasis
| Autor: | Gustavo D. Aguirre, Hélène Léger, Eliot T Smith, N. Adrian Leu, William A. Beltran, Francis C. Luca, Evelyn Santana |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Retinal degeneration Retinal Bipolar Cells PAX6 Transcription Factor Cellular differentiation lcsh:Medicine ELAV-Like Protein 4 Biology Protein Serine-Threonine Kinases Retina Article Transcriptome 03 medical and health sciences chemistry.chemical_compound Interneurons medicine Animals Homeostasis Photoreceptor Cells lcsh:Science Cell Proliferation Regulation of gene expression Mice Knockout Multidisciplinary Kinase lcsh:R AAK1 Retinal medicine.disease Cell biology Mice Inbred C57BL 030104 developmental biology Amacrine Cells chemistry Gene Expression Regulation Knockout mouse lcsh:Q |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-21 (2018) |
| ISSN: | 2045-2322 |
| Popis: | Ndr2/Stk38l encodes a protein kinase associated with the Hippo tumor suppressor pathway and is mutated in a naturally-occurring canine early retinal degeneration (erd). To elucidate the retinal functions of Ndr2 and its paralog Ndr1/Stk38, we generated Ndr1 and Ndr2 single knockout mice. Although retinal lamination appeared normal in these mice, Ndr deletion caused a subset of Pax6-positive amacrine cells to proliferate in differentiated retinas, while concurrently decreasing the number of GABAergic, HuD and Pax6-positive amacrine cells. Retinal transcriptome analyses revealed that Ndr2 deletion increased expression of neuronal stress genes and decreased expression of synaptic organization genes. Consistent with the latter, Ndr deletion dramatically reduced levels of Aak1, an Ndr substrate that regulates vesicle trafficking. Our findings indicate that Ndr kinases are important regulators of amacrine and photoreceptor cells and suggest that Ndr kinases inhibit the proliferation of a subset of terminally differentiated cells and modulate interneuron synapse function via Aak1. |
| Databáze: | OpenAIRE |
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