MINK and TNIK Differentially Act on Rap2-Mediated Signal Transduction to Regulate Neuronal Structure and AMPA Receptor Function
Misshapen/NIKs (Nck-interacting kinases)-related kinase (MINK) and closely related TRAF2/Nck-interacting kinase (TNIK) are proteins that specifically bind to activated Rap2 and are thus hypothesized to relay its downstream signal transduction. Activated Rap2 has been found to stimulate dendritic pru...
| Main Authors: | , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Society for Neuroscience
2011
|
| Online Access: | http://hdl.handle.net/1721.1/64433 |
| _version_ | 1811078856545665024 |
|---|---|
| author | Hussain, Natasha K. Hsin, Honor Huganir, Richard L. Sheng, Morgan Hwa-Tze |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Hussain, Natasha K. Hsin, Honor Huganir, Richard L. Sheng, Morgan Hwa-Tze |
| author_sort | Hussain, Natasha K. |
| collection | MIT |
| description | Misshapen/NIKs (Nck-interacting kinases)-related kinase (MINK) and closely related TRAF2/Nck-interacting kinase (TNIK) are proteins that specifically bind to activated Rap2 and are thus hypothesized to relay its downstream signal transduction. Activated Rap2 has been found to stimulate dendritic pruning, reduce synaptic density and cause removal of synaptic AMPA receptors (AMPA-Rs) (Zhu et al., 2005; Fu et al., 2007). Here we report that MINK and TNIK are postsynaptically enriched proteins whose clustering within dendrites is bidirectionally regulated by the activation state of Rap2. Expression of MINK and TNIK in neurons is required for normal dendritic arborization and surface expression of AMPA receptors. Overexpression of a truncated MINK mutant unable to interact with Rap2 leads to reduced dendritic branching and this MINK-mediated effect on neuronal morphology is dependent upon Rap2 activation. While similarly truncated TNIK also reduces neuronal complexity, its effect does not require Rap2 activity. Furthermore, Rap2-mediated removal of surface AMPA-Rs from spines is entirely abrogated by coexpression of MINK, but not TNIK. Thus, although both MINK and TNIK bind GTP-bound Rap2, these kinases employ distinct mechanisms to modulate Rap2-mediated signaling. MINK appears to antagonize Rap2 signal transduction by binding to activated Rap2. We suggest that MINK interaction with Rap2 plays a critical role in maintaining the morphological integrity of dendrites and synaptic transmission. |
| first_indexed | 2024-09-23T11:06:27Z |
| format | Article |
| id | mit-1721.1/64433 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:06:27Z |
| publishDate | 2011 |
| publisher | Society for Neuroscience |
| record_format | dspace |
| spelling | mit-1721.1/644332022-10-01T01:16:51Z MINK and TNIK Differentially Act on Rap2-Mediated Signal Transduction to Regulate Neuronal Structure and AMPA Receptor Function Hussain, Natasha K. Hsin, Honor Huganir, Richard L. Sheng, Morgan Hwa-Tze Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Sheng, Morgan Hwa-Tze Hussain, Natasha K. Hsin, Honor Sheng, Morgan Hwa-Tze Misshapen/NIKs (Nck-interacting kinases)-related kinase (MINK) and closely related TRAF2/Nck-interacting kinase (TNIK) are proteins that specifically bind to activated Rap2 and are thus hypothesized to relay its downstream signal transduction. Activated Rap2 has been found to stimulate dendritic pruning, reduce synaptic density and cause removal of synaptic AMPA receptors (AMPA-Rs) (Zhu et al., 2005; Fu et al., 2007). Here we report that MINK and TNIK are postsynaptically enriched proteins whose clustering within dendrites is bidirectionally regulated by the activation state of Rap2. Expression of MINK and TNIK in neurons is required for normal dendritic arborization and surface expression of AMPA receptors. Overexpression of a truncated MINK mutant unable to interact with Rap2 leads to reduced dendritic branching and this MINK-mediated effect on neuronal morphology is dependent upon Rap2 activation. While similarly truncated TNIK also reduces neuronal complexity, its effect does not require Rap2 activity. Furthermore, Rap2-mediated removal of surface AMPA-Rs from spines is entirely abrogated by coexpression of MINK, but not TNIK. Thus, although both MINK and TNIK bind GTP-bound Rap2, these kinases employ distinct mechanisms to modulate Rap2-mediated signaling. MINK appears to antagonize Rap2 signal transduction by binding to activated Rap2. We suggest that MINK interaction with Rap2 plays a critical role in maintaining the morphological integrity of dendrites and synaptic transmission. National Institutes of Health (U.S) (MH076936) Canadian Institutes of Health Research 2011-06-15T13:09:55Z 2011-06-15T13:09:55Z 2010-09 2010-08 Article http://purl.org/eprint/type/JournalArticle 0270-6474 http://hdl.handle.net/1721.1/64433 Hussain, Natasha K. et al. “MINK and TNIK Differentially Act on Rap2-Mediated Signal Transduction to Regulate Neuronal Structure and AMPA Receptor Function.” The Journal of Neuroscience 30.44 (2010) : 14786 -14794. en_US http://dx.doi.org/10.1523/jneurosci.4124-10.2010 Journal of Neuroscience Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Society for Neuroscience SFN |
| spellingShingle | Hussain, Natasha K. Hsin, Honor Huganir, Richard L. Sheng, Morgan Hwa-Tze MINK and TNIK Differentially Act on Rap2-Mediated Signal Transduction to Regulate Neuronal Structure and AMPA Receptor Function |
| title | MINK and TNIK Differentially Act on Rap2-Mediated Signal Transduction to Regulate Neuronal Structure and AMPA Receptor Function |
| title_full | MINK and TNIK Differentially Act on Rap2-Mediated Signal Transduction to Regulate Neuronal Structure and AMPA Receptor Function |
| title_fullStr | MINK and TNIK Differentially Act on Rap2-Mediated Signal Transduction to Regulate Neuronal Structure and AMPA Receptor Function |
| title_full_unstemmed | MINK and TNIK Differentially Act on Rap2-Mediated Signal Transduction to Regulate Neuronal Structure and AMPA Receptor Function |
| title_short | MINK and TNIK Differentially Act on Rap2-Mediated Signal Transduction to Regulate Neuronal Structure and AMPA Receptor Function |
| title_sort | mink and tnik differentially act on rap2 mediated signal transduction to regulate neuronal structure and ampa receptor function |
| url | http://hdl.handle.net/1721.1/64433 |
| work_keys_str_mv | AT hussainnatashak minkandtnikdifferentiallyactonrap2mediatedsignaltransductiontoregulateneuronalstructureandampareceptorfunction AT hsinhonor minkandtnikdifferentiallyactonrap2mediatedsignaltransductiontoregulateneuronalstructureandampareceptorfunction AT huganirrichardl minkandtnikdifferentiallyactonrap2mediatedsignaltransductiontoregulateneuronalstructureandampareceptorfunction AT shengmorganhwatze minkandtnikdifferentiallyactonrap2mediatedsignaltransductiontoregulateneuronalstructureandampareceptorfunction |