Adenomatous Polyposis Coli Is Differentially Distributed in Growth Cones and Modulates Their Steering

Koester, Michael P.; Müller, Oliver; Pollerberg, G. Elisabeth

doi:10.1523/jneurosci.2250-07.2007

Cited by 52 publications

(62 citation statements)

References 67 publications

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“…5C). Another downstream target of GSK-3␤ is adenomatous polyposis coli (APC), which promotes microtubule assembly at the growth cone when dephosphorylated (Zhou et al, 2004;Koester et al, 2007;Purro et al, 2008). We found that knockdown of APC also suppressed Dock3-mediated axonal outgrowth after BDNF treatment (Fig.…”

Section: Dock3 Induces Phosphorylation Of Gsk-3␤ At the Plasma Membranementioning

confidence: 82%

“…The importance of CRMPs in axonal formation is highlighted by the evidence that axonal outgrowth is arrested when CRMPs are phosphorylated by some kinases, such as glycogen synthase kinase-3␤ (GSK-3␤), because this phosphorylation causes dissociation of CRMPs from microtubules (Eickholt et al, 2002;Yoshimura et al, 2005). In addition, adenomatous polyposis coli (APC), which promotes microtubule assembly at the growth cone, is another downstream target of GSK-3␤ (Zhou et al, 2004;Koester et al, 2007;Purro et al, 2008), indicating the importance of GSK-3␤ in this dynamic process. In this study, we show that Dock3 binds to GSK-3␤ and inhibits its activity, thereby activating CRMP-2 and APC.…”

Section: Introductionmentioning

confidence: 99%

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Dock3 Stimulates Axonal Outgrowth via GSK-3β-Mediated Microtubule Assembly

Namekata

Harada²,

Guo³

et al. 2012

J. Neurosci.

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Dock3, a new member of the guanine nucleotide exchange factors, causes cellular morphological changes by activating the small GTPase Rac1. Overexpression of Dock3 in neural cells promotes axonal outgrowth downstream of brain-derived neurotrophic factor (BDNF) signaling. We previously showed that Dock3 forms a complex with Fyn and WASP (Wiskott-Aldrich syndrome protein) family verprolinhomologous (WAVE) proteins at the plasma membrane, and subsequent Rac1 activation promotes actin polymerization. Here we show that Dock3 binds to and inactivates glycogen synthase kinase-3␤ (GSK-3␤) at the plasma membrane, thereby increasing the nonphosphorylated active form of collapsin response mediator protein-2 (CRMP-2), which promotes axon branching and microtubule assembly. Exogenously applied BDNF induced the phosphorylation of GSK-3␤ and dephosphorylation of CRMP-2 in hippocampal neurons. Moreover, increased phosphorylation of GSK-3␤ was detected in the regenerating axons of transgenic mice overexpressing Dock3 after optic nerve injury. These results suggest that Dock3 plays important roles downstream of BDNF signaling in the CNS, where it regulates cell polarity and promotes axonal outgrowth by stimulating dual pathways: actin polymerization and microtubule assembly.

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Section: Dock3 Induces Phosphorylation Of Gsk-3␤ At the Plasma Membranementioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Dock3 Stimulates Axonal Outgrowth via GSK-3β-Mediated Microtubule Assembly

Namekata

Harada²,

Guo³

et al. 2012

J. Neurosci.

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“…Here it should be noted that there is a difference between these proteins in the cellular expression profile as well as in axons. APC expression in the retina is known to be markedly reduced at E8 (Koester et al, 2007). In contrast, APC2 expression is sustained at a high level throughout the development of the retina (Fig.…”

Section: Discussionmentioning

confidence: 98%

“…Germ-line mutations in APC are responsible for familial adenomatous polyposis (for review, see Nakamura, 1993). Although APC has been found at sites of cell-cell adhesion in epithelial cells, it also distributes in growth cones in neuronal axons (Shi et al, 2004;Zhou et al, 2004;Koester et al, 2007). APC and APC2 commonly harbor N-terminal dimerization domains, armadillo repeats, ␤-cateninbinding 20 aa repeats, and axin-binding SAMP repeats but have less conserved C-terminal regions (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…APC has been reported to bind directly to microtubules through its COOH(C)-terminal basic region to stabilize them (Munemitsu et al, 1994;Mimori-Kiyosue et al, 2000;Zumbrunn et al, 2001). It has been shown that APC modulates axon steering in vitro (Koester et al, 2007). Moreover, APC is reportedly implicated in the development of the cerebral cortex (Yokota et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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APC2 Plays an Essential Role in Axonal Projections through the Regulation of Microtubule Stability

Shintani¹,

Ihara²,

Tani³

et al. 2009

J. Neurosci.

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Growth cones at the tip of growing axons are key cellular structures that detect guidance cues and mediate axonal growth. An increasing number of studies have suggested that the dynamic regulation of microtubules in the growth cone plays an essential role in growth cone steering. The dynamic properties of microtubules are considered to be regulated by variegated cellular factors but, in particular, through microtubule-interacting proteins. Here, we examined the functional role of adenomatous polyposis coli-like molecule 2 (APC2) in the development of axonal projections by using the chick retinotectal topographic projection system. APC2 is preferentially expressed in the nervous system from early developmental stages through to adulthood. Immunohistochemical analysis revealed that APC2 is distributed along microtubules in growth cones as well as axon shafts of retinal axons. Overexpression of APC2 in cultured cells induced the stabilization of microtubules, whereas the knockdown of APC2 in chick retinas with specific short hairpin RNA reduced the stability of microtubules in retinal axons. APC2 knockdown retinal axons showed abnormal growth attributable to a reduced response to ephrin-A2 in vitro. Furthermore, they showed drastic alterations in retinotectal projections without making clear target zones in the tectum in vivo. These results suggest that APC2 plays a critical role in the development of the nervous system through the regulation of microtubule stability.

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Cytoskeleton in Axon Growth

Stieß

Bradke

2009

Encyclopedia of Life Sciences

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During development, neurons extend two different types of processes, typically several short dendrites and one long axon. The axon forms synapses with dendrites of other neurons to integrate into a neuronal network. Axons can extend to enormous lengths. Their growth is guided and exactly controlled to guarantee the correct neuronal connections. Microtubules and actin filaments, the two major cytoskeletal elements, are the key players in these processes. They form the backbone for axon extension, provide the construction material for axon elongation, and are the site of convergence of extracellular and intrinsic signals. Correct path finding of the axon is ensured by a specialized and highly dynamic structure at the tip of the growing axon, the growth cone. Its dynamic cytoskeleton is the machinery that establishes, controls and directs axon growth. Overall, the cytoskeleton determines the distinction of axons and dendrites and aberrant changes in the cytoskeleton are a major cause of regenerative failure after spinal cord injury. Key concepts: The growth cone is the highly motile tip of a growing axon, where the axon becomes elongated. Growth cone motility is regulated by cytoskeletal dynamics. Actin filaments determine growth cone shape and are involved in path finding. Microtubules give structure to the axon shaft and are essential for axon elongation. Guidance cues act on the cytoskeleton in the growth cone. A dynamic interaction between actin filaments and microtubules is necessary to steer axon growth. The cytoskeleton regulates neuronal polarity. Injury induced pathological changes of the cytoskeleton are a major cause for lack of regeneration after spinal cord injury.

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Adenomatous Polyposis Coli Is Differentially Distributed in Growth Cones and Modulates Their Steering

Cited by 52 publications

References 67 publications

Dock3 Stimulates Axonal Outgrowth via GSK-3β-Mediated Microtubule Assembly

Dock3 Stimulates Axonal Outgrowth via GSK-3β-Mediated Microtubule Assembly

APC2 Plays an Essential Role in Axonal Projections through the Regulation of Microtubule Stability

Cytoskeleton in Axon Growth

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