scholarly journals Absence of persistent spreading, branching, and adhesion in GAP-43-depleted growth cones.

1995 ◽  
Vol 128 (4) ◽  
pp. 647-660 ◽  
Author(s):  
L Aigner ◽  
P Caroni
Keyword(s):  
Growth Factor ◽  
Neurite Outgrowth ◽  
Growth Cone ◽  
Growth Cones ◽  
Culture Conditions ◽  
Major Protein ◽  
Kinase C ◽  
Competence Factor ◽  
Cone Activity

The growth-associated protein GAP-43 is a major protein kinase C substrate of growth cones and developing nerve terminals. In the growth cone, it accumulates near the plasma membrane, where it associates with the cortical cytoskeleton and membranes. The role of GAP-43 in neurite outgrowth is not yet clear, but recent findings suggest that it may be a crucial competence factor in this process. To define the role of GAP-43 in growth cone activity, we have analyzed neurite outgrowth and growth cone activity in primary sensory neurons depleted of GAP-43 by a specific antisense oligonucleotide procedure. Under optimal culture conditions, but in the absence of GAP-43, growth cones adhered poorly, displayed highly dynamic but unstable lamellar extensions, and were strikingly devoid of local f-actin concentrations. Upon stimulation, they failed to produce NGF-induced spreading or insulin-like growth factor-1-induced branching, whereas growth factor-induced phosphotyrosine immunoreactivity and acceleration of neurite elongation were not impaired. Unlike their GAP-43-expressing counterparts, they readily retracted when exposed to inhibitory central nervous system myelin-derived liposomes. Frequency and extent of induced retraction were attenuated by NGF. Our results indicate that GAP-43 can promote f-actin accumulation, evoked morphogenic activity, and resistance to retraction of the growth cone, suggesting that it may promote regulated neurite outgrowth during development and regeneration.

scholarly journals Depletion of 43-kD growth-associated protein in primary sensory neurons leads to diminished formation and spreading of growth cones.

1993 ◽  
Vol 123 (2) ◽  
pp. 417-429 ◽  
Author(s):  
L Aigner ◽  
P Caroni
Keyword(s):  
Neurite Outgrowth ◽  
Growth Cone ◽  
Growth Cones ◽  
Major Protein ◽  
Nerve Terminals ◽  
Drg Neurons ◽  
Process Formation ◽  
Neurite Formation ◽  
Cone Formation ◽  
External Signals

The 43-kD growth-associated protein (GAP-43) is a major protein kinase C (PKC) substrate of growing axons, and of developing nerve terminals and glial cells. It is a highly hydrophilic protein associated with the cortical cytoskeleton and membranes. In neurons it is rapidly transported from the cell body to growth cones and nerve terminals, where it accumulates. To define the role of GAP-43 in neurite outgrowth, we analyzed neurite regeneration in cultured dorsal root ganglia (DRG) neurons that had been depleted of GAP-43 with any of three nonoverlapping antisense oligonucleotides. The GAP-43 depletion procedure was specific for this protein and an antisense oligonucleotide to the related PKC substrate MARCKS did not detectably affect GAP-43 immunoreactivity. We report that neurite outgrowth and morphology depended on the levels of GAP-43 in the neurons in a substrate-specific manner. When grown on a laminin substratum, GAP-43-depleted neurons extended longer, thinner and less branched neurites with strikingly smaller growth cones than their GAP-43-expressing counterparts. In contrast, suppression of GAP-43 expression prevented growth cone and neurite formation when DRG neurons were plated on poly-L-ornithine. These findings indicate that GAP-43 plays an important role in growth cone formation and neurite outgrowth. It may be involved in the potentiation of growth cone responses to external signals affecting process formation and guidance.

scholarly journals Myosin 1c and myosin IIB serve opposing roles in lamellipodial dynamics of the neuronal growth cone

2002 ◽  
Vol 158 (7) ◽  
pp. 1207-1217 ◽  
Author(s):  
Thomas J. Diefenbach ◽  
Vaughan M. Latham ◽  
Dean Yimlamai ◽  
Canwen A. Liu ◽  
Ira M. Herman ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Neurite Outgrowth ◽  
Growth Cone ◽  
Dorsal Root ◽  
Myosin Ii ◽  
Growth Cones ◽  
Neuronal Growth ◽  
Rapid Reduction ◽  
Neuronal Growth Cone

The myosin family of motor proteins is implicated in mediating actin-based growth cone motility, but the roles of many myosins remain unclear. We previously implicated myosin 1c (M1c; formerly myosin Iβ) in the retention of lamellipodia (Wang et al., 1996). Here we address the role of myosin II (MII) in chick dorsal root ganglion neuronal growth cone motility and the contribution of M1c and MII to retrograde F-actin flow using chromophore-assisted laser inactivation (CALI). CALI of MII reduced neurite outgrowth and growth cone area by 25%, suggesting a role for MII in lamellipodial expansion. Micro-CALI of MII caused a rapid reduction in local lamellipodial protrusion in growth cones with no effects on filopodial dynamics. This is opposite to micro-CALI of M1c, which caused an increase in lamellipodial protrusion. We used fiduciary beads (Forscher et al., 1992) to observe retrograde F-actin flow during the acute loss of M1c or MII. Micro-CALI of M1c reduced retrograde bead flow by 76%, whereas micro-CALI of MII or the MIIB isoform did not. Thus, M1c and MIIB serve opposite and nonredundant roles in regulating lamellipodial dynamics, and M1c activity is specifically required for retrograde F-actin flow.

scholarly journals Nitric oxide-induced cardioprotection in cultured rat ventricular myocytes

2000 ◽  
Vol 278 (4) ◽  
pp. H1211-H1217 ◽  
Author(s):  
Roby D. Rakhit ◽  
Richard J. Edwards ◽  
James W. Mockridge ◽  
Anwar R. Baydoun ◽  
Amanda W. Wyatt ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ventricular Myocytes ◽  
Culture Conditions ◽  
Neonatal Rat ◽  
No Donor ◽  
Rat Ventricular Myocytes ◽  
Kinase C ◽  
Neonatal Rat Ventricular Myocytes ◽  
Oxide Synthase

The aim of this study was to investigate the role of nitric oxide (NO) in a cellular model of early preconditioning (PC) in cultured neonatal rat ventricular myocytes. Cardiomyocytes “preconditioned” with 90 min of stimulated ischemia (SI) followed by 30 min reoxygenation in normal culture conditions were protected against subsequent 6 h of SI. PC was blocked by N G-monomethyl-l-arginine monoacetate but not by dexamethasone pretreatment. Inducible nitric oxide synthase (NOS) protein expression was not detected during PC ischemia. Pretreatment (90 min) with the NO donor S-nitroso- N-acetyl-l,l-penicillamine (SNAP) mimicked PC, resulting in significant protection. SNAP-triggered protection was completely abolished by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) but was unaffected by chelerythrine or the presence of glibenclamide and 5-hydroxydecanoate. With the use of RIA, SNAP treatment increased cGMP levels, which were blocked by ODQ. Hence, NO is implicated as a trigger in this model of early PC via activation of a constitutive NOS isoform. After exposure to SNAP, the mechanism of cardioprotection is cGMP dependent but independent of protein kinase C or ATP-sensitive K+ channels. This differs from the proposed mechanism of NO-induced cardioprotection in late PC.

The role of transcription-dependent priming in nerve growth factor promoted neurite outgrowth

1982 ◽  
Vol 91 (2) ◽  
pp. 305-316 ◽  
Author(s):  
Lloyd A. Greene ◽  
David E. Burstein ◽  
Mark M. Black
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neurite Outgrowth ◽  
Nerve Growth
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