Cdh1-APC Controls Axonal Growth and Patterning in the Mammalian Brain

Konishi, Yoshiyuki; Stegmüller, Judith; Matsuda, Takehisa; Bonni, Shirin; Bonni, Azad

doi:10.1126/science.1093712

Cited by 344 publications

(409 citation statements)

References 22 publications

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“…One elegant mechanism has been defined involving the anaphase promoting complex (APC), which functions as an E3 ubiquitin ligase in the regulation of cyclins and other mediators of cell-cycle control. In postmitotic neurons, APC and its activator protein, Cdh1, stimulate degradation of the transcription factor SnoN (Konishi et al 2004;Stegmuller et al 2006). SnoN levels are also regulated by TGF-b/SMAD-2 signaling (Stegmuller et al 2008).…”

Section: Transcription Regulatorsmentioning

confidence: 99%

Initiating and Growing an Axon

Polleux¹,

Snider²

2010

Cold Spring Harbor Perspectives in Biology

161

127

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The ability of neurons to form a single axon and multiple dendrites underlies the directional flow of information transfer in the central nervous system. Dendrites and axons are molecularly and functionally distinct domains. Dendrites integrate synaptic inputs, triggering the generation of action potentials at the level of the soma. Action potentials then propagate along the axon, which makes presynaptic contacts onto target cells. This article reviews what is known about the cellular and molecular mechanisms underlying the ability of neurons to initiate and extend a single axon during development. Remarkably, neurons can polarize to form a single axon, multiple dendrites, and later establish functional synaptic contacts in reductionist in vitro conditions. This approach became, and remains, the dominant model to study axon initiation and growth and has yielded the identification of many molecules that regulate axon formation in vitro (Dotti et al. 1988). At present, only a few of the genes identified using in vitro approaches have been shown to be required for axon initiation and outgrowth in vivo. In vitro, axon initiation and elongation are largely intrinsic properties of neurons that are established in the absence of relevant extracellular cues. However, the importance of extracellular cues to axon initiation and outgrowth in vivo is emerging as a major theme in neural development (Barnes and Polleux 2009). In this article, we focus our attention on the extracellular cues and signaling pathways required in vivo for axon initiation and axon extension.

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Section: Transcription Regulatorsmentioning

confidence: 99%

Initiating and Growing an Axon

Polleux¹,

Snider²

2010

Cold Spring Harbor Perspectives in Biology

161

127

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“…As in the budding yeast model, where the first phase of Clb2 degradation by APC Cdc20 (Ba¨umer et al, 2000;Yeong et al, 2000;Wa¨sch and Cross, 2002) is already sufficient for most aspects of mitotic exit (Wa¨sch and Cross, 2002), the main role of Cdh1 perhaps in concert with CKIs like p21 and p27 in mammalian cells is also very likely the regulation of a stable G1 and accurate DNA replication by keeping mitotic cyclins low during G1 (Figure 3). APC Cdh1 may also play an important role in differentiation, since it controls axonal growth and morphogenesis in postmitotic neurons in mammalian cells (Konishi et al, 2004). APC Cdh1 has also been linked to TGF -mediated control of cell growth and differentiation (Stroschein et al, 2001;Wan et al, 2001).…”

Section: Proteolysis and Cell Cycle Controlmentioning

confidence: 99%

Anaphase-promoting complex-dependent proteolysis of cell cycle regulators and genomic instability of cancer cells

2005

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“…Konishi et al (2004) has shown that anaphase promoting complex plays an important role in transcriptional regulation of axon growth. This complex is a multisubunit ubiquitin ligase that functions in mitotic cells to promote cell cycle exit via degradation of cyclins and other regulators of cell cycle progression (see Murray 2004 for a recent review).…”

Section: Genetic Control Of Axon Growthmentioning

confidence: 99%

Intracellular control of developmental and regenerative axon growth

Zhou

Snider

2006

Phil. Trans. R. Soc. B

174

138

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Axon growth is a highly regulated process that requires stimulating signals from extracellular factors. The extracellular signals are then transduced to regulate coordinately gene expression and local axon assembly. Growth factors, especially neurotrophins that act via receptor tyrosine kinases, have been heavily studied as extracellular factors that stimulate axon growth. Downstream of receptor tyrosine kinases, recent studies have suggested that phosphatidylinositol-3 kinase (PI3K) regulates local assembly of axonal cytoskeleton, especially microtubules, via glycogen synthase kinase 3b (GSK-3b) and multiple microtubule binding proteins. The role of extracellular signal regulated kinase (ERK) signalling in regulation of local axon assembly is less clear, but may involve the regulation of local protein translation. Gene expression during axon growth is regulated by transcription factors, among which cyclic AMP response element binding protein and nuclear factors of activated T-cells (NFATs) are known to be required for neurotrophin (NT)-induced axon extension. In addition to growth factors, extracellular matrix molecules and neuronal activity contribute importantly to control axon growth. Increasingly, evidence suggests that these influences act to enhance growth via coordinating with growth factor signalling. Finally, evidence is emerging that developmental versus regenerative axon growth may be mediated by distinct signalling pathways, both at the level of gene transcription and at the level of local axon assembly.

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Cdh1-APC Controls Axonal Growth and Patterning in the Mammalian Brain

Cited by 344 publications

References 22 publications

Initiating and Growing an Axon

Initiating and Growing an Axon

Anaphase-promoting complex-dependent proteolysis of cell cycle regulators and genomic instability of cancer cells

Intracellular control of developmental and regenerative axon growth

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