Neuroprotection by neurotrophic factors and membrane depolarization is regulated by calmodulin kinase IV
Pérez García, María José
Pablo Llavall, Yolanda de
Comella i Carnicé, Joan Xavier
MetadataShow full item record
Neurotrophic factors promote motoneuron (MN) survival through increased intracellular calcium (Ca(2+)) and regulation of the phosphatidylinositol (PI) 3-kinase/protein kinase B (PKB) pathway by calmodulin (CaM). Activation of the PI 3-kinase/PKB pathway is one of the well established mechanisms involved
in MN survival. The Ca(2+)/CaM complex interacts with and modulates the functionality of a large number of proteins, including serine/threonine protein kinases such as Ca(2+)/CaM-dependent protein kinases (CaMKs). Using a primary culture of embryonic chicken spinal cord MNs, we investigated the role of CaMKIV in mediating this process. We cloned chicken CaMKIV and demonstrated its expression in purified MNs by means of reverse transcription-PCR, Western blot, and immunofluorescence. Using RNA interference, we show that endogenous CaMKIV mediates cell survival induced by neurotrophic factors or membrane depolarization. The survival effect is independent of CaMKIV kinase activity; however, CaMKIV functionality depends on the presence of Ca(2+)/CaM. Finally, CaMKIV associates to the p85 subunit of PI 3-kinase in a Ca(2+)-dependent manner, suggesting a role in regulating PI 3-kinase/PKB activation.
Is part ofJournal of Biological Chemistry, 2008, vol. 283, núm. 7, p. 4133-4144
Showing items related by title, author, creator and subject.
The death receptor antagonist FLIP-L interacts with Trk and is necessary for neurite outgrowth induced by neurotrophins Moubarak, Rana S.; Solé Serra, Carme; Pascual, Marta; Gutierrez, Humberto; Llovera i Tomàs, Marta; Pérez García, María José; Gozzelino, Raffaella; Segura Ginard, Miguel Francisco; Iglesias Guimarais, Victoria; Reix, Stéphanie; Soler i Tatché, Rosa Ma.; Davies, Alun M.; Soriano, Eduardo; Yuste Mateos, Víctor J. (Víctor José); Comella i Carnicé, Joan Xavier (Society for Neuroscience, 2010)FLICE-inhibitory protein (FLIP) is an endogenous inhibitor of the signaling pathway triggered by the activation of death receptors. Here, we reveal a novel biological function for the long form of FLIP (FLIP-L) in neuronal ...
Activation of Phosphatidylinositol 3-Kinase, but Not Extracellular-Regulated Kinases, Is Necessary to Mediate BrainDerived Neurotrophic Factor-Induced Motoneuron Survival Dolcet Roca, Xavier; Egea Navarro, Joaquim; Soler i Tatché, Rosa Ma.; Martin-Zanca, Dionisio; Comella i Carnicé, Joan Xavier (Wiley, 1999)Chick embryo spinal cord motoneurons develop a trophic response to some neurotrophins when they are maintained in culture in the presence of muscle extract. Thus, after 2 days in culture, brain-derived neurotrophic factor ...
Ubiquitination of TrkA by Nedd4-2 regulates receptor lysosomal targeting and mediates receptor signaling Georgieva, Maya V.; Pablo Llavall, Yolanda de; Sanchis, Daniel; Comella i Carnicé, Joan Xavier; Llovera i Tomàs, Marta (Wiley, 2011)The nerve growth factor receptor TrkA (tropomyosin-related kinase receptor) participates in the survival and differentiation of several neuronal populations. The C-terminal tail of TrkA contains a PPXY motif, the binding ...