A shift in protein S-palmitoylation, with persistence of growth-associated substrates, marks a critical period for synaptic plasticity in developing brain

Patterson, Sean I.; Skene, J. H. Pate

doi:10.1002/(sici)1097-4695(19990605)39:3<423::aid-neu8>3.0.co;2-z

Cited by 26 publications

(28 citation statements)

References 87 publications

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“…7A) is most likely associated with the formation of cortical synapses in layer II/III (Lendvai et al, 2000) and development of intracortical projections (Miller et al, 2001), both of which occur at that time. After P15, the decrease in GAP-43 levels of WT mice may coincide with the molecular maturation of cortical synapses (Patterson and Skene, 1999).…”

Section: Regulation Of Gap-43 Expression With Respect To Developmentamentioning

confidence: 99%

GAP‐43 heterozygous mice show delayed barrel patterning, differentiation of radial glia, and downregulation of GAP‐43

McIlvain

McCasland

2006

Anat. Rec.

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GAP-43 heterozygous (HZ) mice exhibit abnormal thalamocortical pathfinding, fasciculation, and terminal arborization at postnatal day 7 (P7). Here we tested whether these defects are correlated with delayed development of HZ cortical patterns. We assessed the rate of barrel segregation and radial glia differentiation in wild-type (WT) and HZ cortices. Since GAP-43 is involved in some forms of neural plasticity, we also compared the duration of the critical period for lesion-induced plasticity in both genotypes. Cytochrome oxidase histochemistry revealed a delay of approximately 1 day in barrel pattern formation in GAP-43 HZ mice. GAP-43 WT barrels showed complete segregation between P2-P3, while HZ barrels did not reach the same level of segregation until P3-P4. We found a similar delay in the transformation of radial glia from monopolar to multipolar phenotypes, from P5 in WT to P7 in HZ cortex. Radial glial cells represent many of the neuronal progenitors in developing cortex and aid in cell migration. Thus, the delay in radial glial differentiation may contribute to the delay in HZ barrel segregation. Interestingly, we found no change in the extent of the critical period for HZ cortical responsiveness to early peripheral damage or in the time course of the cortical response. As expected, GAP-43 expression in HZ cortex is significantly reduced early in development. However, HZ GAP-43 expression remains at maximum levels after P9, when it is normally downregulated. As a result, HZ GAP-43 expression is near-normal by P26, by which time near-normal barrel dimensions have been restored. Our findings indicate that GAP-43 deficiency leads to early delays in barrel development and suggest that these failures are followed by homeostatic responses, including prolonged GAP-43 expression. These compensatory mechanisms may rescue normal cortical reorganization in neonates and nearnormal barrel morphology and GAP-43 expression in adulthood.

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Section: Regulation Of Gap-43 Expression With Respect To Developmentamentioning

confidence: 99%

GAP‐43 heterozygous mice show delayed barrel patterning, differentiation of radial glia, and downregulation of GAP‐43

McIlvain

McCasland

2006

Anat. Rec.

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“…The pellet contained pure synaptosomes (Syn). Synaptosomes were prepared from different developmental ages as previously described (Patterson and Skene, 1999) by a modification of the Ficoll flotation method (Gordon-Weeks, 1987).…”

Section: Subcellular Fractionationmentioning

confidence: 99%

The neuronal Arf GAP centaurin α1 modulates dendritic differentiation

Moore

Thacker

Larimore

et al. 2007

Journal of Cell Science

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ReferencesAggensteiner, M. and Reiser, G. (2003). Expression of the brain-specific membrane adapter protein p42 IP4 /centaurin a, a Ins(1,3,4,5)P 4 /PtdIns(3,4,5)P 3 binding protein, in developing rat brain. Brain Res. Dev. Brain Res. 142,[77][78][79][80][81][82][83][84][85][86][87]. Albertinazzi, C., Za, L., Paris, S. and de Curtis, I. (2003). ADP-ribosylation factor 6 and a functional PIX/p95-APP1 complex are required for Rac1B-mediated neurite outgrowth. Mol. Biol. Cell 14, 1295-1307. Allen, P., Ouimet, C. and Greengard, P. (1997 (1996). Identification and cloning of centaurin alpha: a novel phosphatidylinositol (3,4,5)-trisphosphate binding protein from rat brain.

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“…Indeed, high levels of expression of proteins containing the FIMs such as GAP-43 and paralemmin persist in the adult nervous system, in regions that have been associated with high plasticity (Routtenberg, 1987;Kutzleb et al, 1998). Recent data show a dramatic decrease in GAP-43 palmitoylation during early neuronal development, suggesting that protein acylation may serve as a dynamic regulator of axonal extension and synapse formation (Patterson and Skene, 1999). Moreover, blocking protein palmitoylation by cerulenin disrupts the morphogenic effects induced by GAP-43 (DeJesus and Bizzozero, 2002).…”

Section: Possible Roles In Synaptogeneismentioning

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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A shift in protein S-palmitoylation, with persistence of growth-associated substrates, marks a critical period for synaptic plasticity in developing brain

Cited by 26 publications

References 87 publications

GAP‐43 heterozygous mice show delayed barrel patterning, differentiation of radial glia, and downregulation of GAP‐43

GAP‐43 heterozygous mice show delayed barrel patterning, differentiation of radial glia, and downregulation of GAP‐43

The neuronal Arf GAP centaurin α1 modulates dendritic differentiation

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

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