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Growth Cone Formation (growth + cone_formation)
Selected AbstractsInitial stages of neural regeneration in Helisoma trivolvis are dependent upon PLA2 activityDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2003Matthew S. Geddis Abstract Neuronal regeneration after damage to an axon tract requires the rapid sealing of the injured plasma membrane and the subsequent formation of growth cones that can lead regenerating processes to their appropriate target. Membrane sealing and growth cone formation are Ca2+ -dependent processes, but the signaling pathways activated by Ca2+ to bring about these effects remain poorly understood. An in vitro injury model was employed in which neurites from identified snail neurons (Helisoma trivolvis) were transected with a glass microknife, and the formation of new growth cones from the distal portions of transected neurites was recorded at defined times after transection. This study presents three main results. First, phospholipase A2 (PLA2), a calcium-activated enzyme, is necessary for membrane sealing in vitro. Second, PLA2 activity is also required for the formation of a new growth cone after the membrane has sealed successfully. Thus, PLA2 plays a dual role by affecting both growth cone formation and membrane sealing. Third, the injury-induced activation of PLA2 by Ca2+ controls growth cone formation through the production of leukotrienes, secondary metabolites of PLA2 activity. Taken together, these results suggest that the injury-induced Ca2+ influx acts via PLA2 and leukotriene production to assure growth cone formation. These findings indicate that events that cause an inhibition of PLA2 or lipoxygenases, enzymes that produce leukotrienes, could result in the inability of neurites to regenerate. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 555,565, 2003 [source] Participation of protein kinase C , isoform and extracellular signal-regulated kinase in neurite outgrowth of GT1 hypothalamic neuronsJOURNAL OF NEUROCHEMISTRY, Issue 6 2002Youngshik Choe Abstract In the present study, we investigated the selective role of protein kinase C (PKC) isoforms on neurite outgrowth of the GT1 hypothalamic neurons using several PKC isoform-selective inhibitors and transfection-based expression of enhanced green fluorescence protein (EGFP)-fused PKC isoforms. 12- O -Tetradecanoylphorbol-13-acetate (TPA) induced neurite outgrowth and growth cone formation, effects that were blocked by GF 109203X (a PKC inhibitor), safingolTM(a PKC,-selective inhibitor), but not by rottlerinTM (a PKC,-selective inhibitor), indicating that PKC, may be selectively involved in neurite outgrowth and cytoskeletal changes of filamentous actin and ,-tubulin. To define the differential localization of PKC isoforms, EGFP-tagged PKC,, PKC,, and PKC, were transfected into GT1 neuronal cells. TPA treatment induced relocalization of PKC,-EGFP to growth cones and cell,cell adhesion sites, PKC,-EGFP to the nucleus, and PKC,-EGFP to the membrane ruffle, respectively. An EGFP chimera of the catalytic domain of PKC, (PKC,-Cat-EGFP), the expression of which was inducible by doxycycline, was employed to directly ascertain the effect of PKC, enzymatic activity on neurite outgrowth of GT1 cells. Transient transfection of PKC,-Cat-EGFP alone increased the neurite-outgrowth and doxycycline treatment further augmented the number of neurite-containing cells. We also examined the involvement of the extracellular signal-regulated kinase (ERK) MAP kinase in TPA-induced neurite outgrowth. TPA treatment increased phosphorylated ERK MAP kinase, but not p38 MAP kinase. Specific inhibition of PKC, with safingol blocked the phosphorylation of ERK induced by TPA. More importantly, both neurite outgrowth and phosphorylation of ERK by TPA were blocked by PD 098059, a specific inhibitor of MEK (MAP kinase/ERK kinase-1), but not by SB203580, a specific inhibitor of p38 MAP kinase. These results demonstrate that PKC, isoform-specific activation is involved in neurite outgrowth of GT1 hypothalamic neuronal cells via ERK, but not the p38 MAP kinase signal pathway. [source] The FE65 proteins and Alzheimer's diseaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2008Declan M. McLoughlin Abstract The FE65s (FE65, FE65L1, and FE65L2) are a family of multidomain adaptor proteins that form multiprotein complexes with a range of functions. FE65 is brain-enriched, whereas FE65L1 and FE65L2 are more widely expressed. All three members contain a WW domain and two PTB domains. Through the PTB2 domain, they all interact with the Alzheimer's disease amyloid precursor protein (APP) intracellular domain (AICD) and can alter APP processing. After sequential proteolytic processing of membrane-bound APP and release of AICD to the cytoplasm, FE65 can translocate to the nucleus to participate in gene transcription events. This role is further mediated by interactions of FE65 PTB1 with the transcription factors CP2/LSF/LBP1 and Tip60 and the WW domain with the nucleosome assembly factor SET. However, FE65 target genes have not yet been confirmed. The FE65 PTB1 domain also interacts with two cell surface lipoproteins receptors, the low-density lipoprotein receptor-related protein (LRP) and ApoEr2, forming trimeric complexes with APP. The FE55 WW domain also binds to mena, through which it functions in regulation of the actin cytoskeleton, cell motility, and neuronal growth cone formation. While single knockout mice appear normal, double FE65,/,/FE65L1,/, mice have substantial neurodevelopmental defects. These include heterotopic neurons and axonal pathfinding defects, findings similar to findings in both Mena and triple APP:APLP1:APLP2 knockout mice and also lissencephalopathies in humans. Thus APPs, FE65s, and mena may act together in a developmental signalling pathway. This article reviews the known functions of the FE65 family and their role in APP function and Alzheimer's disease. © 2007 Wiley-Liss, Inc. [source] Melatonin induces neuritogenesis at early stages in N1E-115 cells through actin rearrangements via activation of protein kinase C and Rho-associated kinaseJOURNAL OF PINEAL RESEARCH, Issue 3 2007Alfredo Bellon Abstract:, Melatonin increases neurite formation in N1E-115 cells through microtubule enlargement elicited by calmodulin antagonism and vimentin intermediate filament reorganization caused by protein kinase C (PKC) activation. Microfilament rearrangement is also a necessary process in growth cone formation during neurite outgrowth. In this work, we studied the effect of melatonin on microfilament rearrangements present at early stages of neurite formation and the possible participation of PKC and the Rho-associated kinase (ROCK), which is a downstream kinase in the PKC signaling pathway. The results showed that 1 nm melatonin increased both the number of cells with filopodia and with long neurites. Similar results were obtained with the PKC activator phorbol 12-myristate 13-acetate (PMA). Both melatonin and PMA increased the quantity of filamentous actin. In contrast, the PKC inhibitor bisindolylmaleimide abolished microfilament organization elicited by either melatonin or PMA, while the Rho inhibitor C3, or the ROCK inhibitor Y27632, abolished the bipolar neurite morphology of N1E-115 cells. Instead, these inhibitors prompted neurite ramification. ROCK activity measured in whole cell extracts and in N1E-115 cells was increased in the presence of melatonin and PMA. The results indicate that melatonin increases the number of cells with immature neurites and suggest that these neurites can be susceptible to differentiation by incoming extracellular signals. Data also indicate that PKC and ROCK are involved at initial stages of neurite formation in the mechanism by which melatonin recruits cells for later differentiation. [source] | ||||||||||