G0 is a major growth cone protein subject to regulation by GAP-43

Strittmatter, Stephen M.; Valenzuela, Dario; Kennedy, Timothy E.; Neer, Eva J.; Fishman, Mark C.

doi:10.1038/344836a0

Cited by 425 publications

(256 citation statements)

References 56 publications

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“…Thus, the presence of FIMs in proteins such as GAP-43 and paralemmin that regulate process outgrowth strongly suggest functional relevance. Previous studies indicate that the first 10 amino acids of GAP-43 are sufficient to induce filopodia and to stimulate G o (Strittmatter et al, 1990;Sudo et al, 1992;Arni et al, 1998). Surprisingly, synthetic di-palmitoylated peptides, which include the N-terminal sequences of GAP-43 abolished G o activity (Strittmatter et al, 1994a).…”

Section: Possible Mechanisms For Induction Of Process Outgrowth By Fimsmentioning

confidence: 99%

Regulation of Dendritic Branching and Filopodia Formation in Hippocampal Neurons by Specific Acylated Protein Motifs

Gauthier-Campbell

Bredt

Murphy

et al. 2004

MBoC

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Although neuronal axons and dendrites with their associated filopodia and spines exhibit a profound cell polarity, the mechanism by which they develop is largely unknown. Here, we demonstrate that specific palmitoylated protein motifs, characterized by two adjacent cysteines and nearby basic residues, are sufficient to induce filopodial extensions in heterologous cells and to increase the number of filopodia and the branching of dendrites and axons in neurons. Such motifs are present at the N-terminus of GAP-43 and the C-terminus of paralemmin, two neuronal proteins implicated in cytoskeletal organization and filopodial outgrowth. Filopodia induction is blocked by mutations of the palmitoylated sites or by treatment with 2-bromopalmitate, an agent that inhibits protein palmitoylation. Moreover, overexpression of a constitutively active form of ARF6, a GTPase that regulates membrane cycling and dendritic branching reversed the effects of the acylated protein motifs. Filopodia induction by the specific palmitoylated motifs was also reduced upon overexpression of a dominant negative form of the GTPase cdc42. These results demonstrate that select dually lipidated protein motifs trigger changes in the development and growth of neuronal processes. INTRODUCTIONNeurons possess an elaborate plasma membrane architecture that includes axons, dendrites, and synaptic sites (Da Silva and Dotti, 2002). Modulation of the plasma membrane shape and composition regulate processes outgrowth, axonal development, dendritic branching, and the construction of synapses (Jontes and Smith, 2000). These changes are regulated by interactions between the constituents of the plasma membrane, the exo/endocytic vesicles, and the cytoskeleton (Wood and Martin, 2002). In nonneuronal cells, differential modulation of membrane flow can result in the formation of processes such as microspikes, lamellopodia, and filopodia (Wood and Martin, 2002). However, factors that regulate the formation and maintenance of specific classes of membranous processes in neuronal cells remain poorly understood.Dendritic filopodia, cell surface extensions filled with tight parallel bundles of actin filaments, are thought to be precursors for developing synapses (Dailey and Smith, 1996;Small, 1988). Filopodia are typically 5-35 m in length and rapidly alter their position and shape. In developing axons, filopodia occur at the tips of growth cones and may aid the axon in finding its appropriate target. In dendrites, filopodia act as precursors to spines, short bulbous protrusions of the dendrite that form excitatory postsynaptic contacts on many neurons (Jontes and Smith, 2000). Thus, changes in membrane structure that result in the formation of filopodia are likely important in axonal guidance and spine formation. In contrast, dendritic branching is thought to be mediated via an actin and/or microtubule-dependent mechanisms (Jan and Jan, 2003). Recent studies showed that in early neuronal development dendrites originate from lamellopodia and short neurites (Jan and Jan, ...

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Section: Possible Mechanisms For Induction Of Process Outgrowth By Fimsmentioning

confidence: 99%

Regulation of Dendritic Branching and Filopodia Formation in Hippocampal Neurons by Specific Acylated Protein Motifs

Gauthier-Campbell

Bredt

Murphy

et al. 2004

MBoC

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“…It should be added, that at least in case of certain proteins, interaction with caveolin-1 was proposed to attenuate their signaling activity [23]. In case of GAP-43 interacting with many proteins, including G 0 [12], calmodulin [13] and PKCd [24], co-localization with caveolin-1 could affect the downstream pathways, especially since we observed decreased phosphorylation of GAP-43 [14] and inhibited interaction with PKCd [8] upon accumulation of palmitoylcarnitine.…”

Section: Discussionmentioning

confidence: 75%

Palmitoylcarnitine regulates estrification of lipids and promotes palmitoylation of GAP‐43

Nałęcz¹,

Szczepankowska²,

Czeredys³

et al. 2007

FEBS Letters

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Palmitoylcarnitine was previously shown to promote differentiation of neuroblastoma NB-2a cells. It was also observed to increase palmitoylation of several proteins and to diminish incorporation of palmitic acid to phospholipids, as well as to affect growth associated protein GAP-43 by decreasing its phosphorylation and interaction with protein kinase C. The present study was focused on influence of palmitoylcarnitine on palmitoylation of GAP-43 and lipid metabolism. Althought palmitoylcarnitine did not significantly affect the total phospholipids and fatty acid content, it increased incorporation of palmitate moiety to triacylglicerides and cholesterol esters, with a decrease of free cholesterol content. The presence of palmitoylcarnitine significantly increased the amount of covalently bound palmitate to GAP-43, which can regulate the signal transduction pathways.

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“…As mentioned earlier, Go is the most abundant heterotrimeric G protein in brain [2] and one of the major membrane components in the growth cone [39]. Overexpression of Goα promotes neuritogenesis in several neuroblastoma cell lines, including PC12, N1E115 and Neuro2a cells [40,41].…”

Section: Discussionmentioning

confidence: 99%

The alpha subunit of Go interacts with promyelocytic leukemia zinc finger protein and modulates its functions

Won¹,

Park²,

Ju³

et al. 2008

Cellular Signalling

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G0 is a major growth cone protein subject to regulation by GAP-43

Cited by 425 publications

References 56 publications

Regulation of Dendritic Branching and Filopodia Formation in Hippocampal Neurons by Specific Acylated Protein Motifs

Regulation of Dendritic Branching and Filopodia Formation in Hippocampal Neurons by Specific Acylated Protein Motifs

Palmitoylcarnitine regulates estrification of lipids and promotes palmitoylation of GAP‐43

The alpha subunit of Go interacts with promyelocytic leukemia zinc finger protein and modulates its functions

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