Publications (2)9.47 Total impact
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Article: Ankyrin repeat-rich membrane spanning protein (kidins220) is required for neurotrophin and ephrin receptor-dependent dendrite development.
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ABSTRACT: Dendrites are the primary sites on neurons for receiving and integrating inputs from their presynaptic partners. Defects in dendrite development perturb the formation of neural circuitry and impair information processing in the brain. Extracellular cues are important for shaping the dendritic morphogenesis, but the underlying molecular mechanisms are not well understood. In this study, we examined the role of ARMS (ankyrin repeat-rich membrane spanning protein), also known as Kidins220 (kinase D-interacting substrate of 220 kDa), previously identified as a downstream target of neurotrophin and ephrin receptors, in dendrite development. We report here that knockdown of ARMS/Kidins220 by in utero electroporation impairs dendritic branching in mouse cerebral cortex, and silencing of ARMS/Kidins220 in primary rat hippocampal neurons results in a significant decrease in the length, number, and complexity of the dendritic arbors. Overexpression of cell surface receptor tyrosine kinases, including TrkB and EphB2, in ARMS/Kidins220-deficient neurons can partially rescue the defective dendritic phenotype. More importantly, we show that PI3K (phosphoinositide-3-kinase)- and Akt-mediated signaling pathway is crucial for ARMS/Kidins220-dependent dendrite development. Furthermore, loss of ARMS/Kidins220 significantly reduced the clustering of EphB2 receptor signaling complex in neurons. Our results collectively suggest that ARMS/Kidins220 is a key player in organizing the signaling complex to transduce the extracellular stimuli to cellular responses during dendrite development.Journal of Neuroscience 06/2012; 32(24):8263-9. · 7.11 Impact Factor -
Article: Cyclin-dependent kinase 5 in axon growth and regeneration.
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ABSTRACT: Injury to the central nervous system often leads to irreversible deficits because of the failure of damaged axons to regrow and restore the functional neural circuitry. Coordinated orchestration of multiple cellular processes including cytoskeletal dynamics and gene expression are essential for both developmental and regenerative axon growth. Recently, mounting evidence suggests that cyclin-dependent kinase 5 (Cdk5), a neuronal kinase implicated in almost all aspects of brain development and function, regulates multiple players required for axon formation and regeneration. Indeed, Cdk5 functions as a "plastic" kinase that maintains the axon growth ability by enabling efficient cytoskeletal reorganization, enhancing protein translation, reducing protein degradation, and promoting injury-induced gene transcription. Here, we summarize the up-to-date information on the mechanisms underlying the axon growth and regeneration after injury.International Review of Neurobiology 01/2012; 105:91-115. · 2.35 Impact Factor
