2016
DOI: 10.1016/j.neuropharm.2016.03.050
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Kalirin is required for BDNF-TrkB stimulated neurite outgrowth and branching

Abstract: Exogenous brain-derived neurotrophic factor (BDNF), acting through TrkB, is known to promote neurite formation and branching. This response to BDNF was eliminated by inhibition of TrkB kinase and by specific inhibition of the GEF1 domain of Kalirin, which activates Rac1. Neurons from Kalrn knockout mice were unable to activate Rac1 in response to BDNF. BDNF-triggered neurite outgrowth was abolished when Kalrn expression was reduced using shRNA that targets all of the major Kalrn isoforms, and reduced in neuron… Show more

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Cited by 29 publications
(42 citation statements)
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References 87 publications
(172 reference statements)
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“…Dora-Rac1, a FRET biosensor for Rac1, was used to evaluate Rac1 activation in cells expressing each Kal7 mutant 58, 89 . Briefly, vector encoding the Dora-Rac1 biosensor and various amounts of vector encoding Myc-tagged Kalirin or KalGEF1 were transfected into HEK293 cells.…”
Section: Methodsmentioning
confidence: 99%
See 1 more Smart Citation
“…Dora-Rac1, a FRET biosensor for Rac1, was used to evaluate Rac1 activation in cells expressing each Kal7 mutant 58, 89 . Briefly, vector encoding the Dora-Rac1 biosensor and various amounts of vector encoding Myc-tagged Kalirin or KalGEF1 were transfected into HEK293 cells.…”
Section: Methodsmentioning
confidence: 99%
“…Phosphorylated bKal7 was prepared for mass spec analysis as described for SR7:9; pY1123 was the major site identified. Based on the rosette screen and the biologically significant role played by Kalirin in TrkB signaling 58 , a subset of 12 GST-SH2 and -PTB domains were tested for their ability to bind to bKal7 phosphorylated in vitro by recombinant TrkB kinase. For Western blotting, TrkB-treated and untreated bKal7 proteins were separated on 4-12 % NuPAGE gels (Invitrogen), transferred to nitrocellulose, and probed with antibodies to phosphotyrosine (Cell Signaling), Kalirin 22 and phosphorylated TrkB /pY816 (Ab75173, Abcam).…”
Section: Methodsmentioning
confidence: 99%
“…Since levels of Kal9 and Kal12, which play essential roles in neurite extension and branching early in development, rise in Kal7 KO mice [29, 30], it seemed possible that changes in these isoforms could contribute to the exaggerated responses to cocaine availability or administration. If so, the response of KalSR KO mice to cocaine would be expected to differ from the response of Kal7 KO mice.…”
Section: Resultsmentioning
confidence: 99%
“…These transcript isoforms also differs in the spatio-temporal expression pattern as seen in Kalrn7 found in the adult brain and Kalrn9 and 12 predominantly expressed during development. Kalirin protein isoforms seem to respond to a variety of signals including Nerve Growth Factor signaling through the TrkB receptor, BDNF signaling through Rac1 (Chakrabarti et al, 2005; Yan et al, 2016). It also interacts with many PDZ domain containing proteins such as PSD95 (Penzes et al, 2001).…”
Section: Discussionmentioning
confidence: 99%