MINK and TNIK differentially act on Rap2-mediated signal transduction to regulate neuronal structure and AMPA receptor function

Natasha K. Hussain, Honor Hsin, Richard L Huganir, Morgan Sheng

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)14786-14794
Number of pages9
JournalJournal of Neuroscience
Volume30
Issue number44
DOIs
StatePublished - Nov 3 2010

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TNF Receptor-Associated Factor 2
AMPA Receptors
Signal Transduction
Phosphotransferases
Neuronal Plasticity
Dendrites
Neurotransmitter Receptor
Guanosine Triphosphate
Synaptic Transmission
Protein Kinases
Cluster Analysis
Spine
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

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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.

In: Journal of Neuroscience, Vol. 30, No. 44, 03.11.2010, p. 14786-14794.

Research output: Contribution to journalArticle

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