Induction of microtubule-associated protein 1B expression in Schwann cells during nerve regeneration

Ma, Dongling; Chow, S. Y.; Obrocka, Maria; Connors, Theresa; Fischer, Itzhak

doi:10.1016/s0006-8993(99)01148-8

Cited by 33 publications

(36 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The fact that the delayed decline of MAP1B temporally associates with the most severe dendritic spine abnormality in the Fmr1 KO neurons in vivo also indicates the functional importance of MAP1B down-regulation in synapse development. At the adult stage, low levels of MAP1B expression is limited to brain neurons that are prone to drug and͞or lesion induced plasticity (47,48). In this regard, although misregulated MAP1B expression was more obviously detected in Fmr1 hippocampus in neonates (Fig.…”

Section: Discussionmentioning

confidence: 93%

The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development

Wang

Liang

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

288

266

View full text Add to dashboard Cite

The fragile X mental retardation protein (FMRP) is a selective RNA-binding protein implicated in regulating translation of its mRNA ligands. The absence of FMRP results in fragile X syndrome, one of the leading causes of inherited mental retardation. Delayed dendritic spine maturation was found in fragile X mental retardation patients as well as in Fmr1 knockout (KO) mice, indicating the functional requirement of FMRP in synaptic development. However, the biochemical link between FMRP deficiency and the neuronal impairment during brain development has not been defined. How FMRP governs normal synapse development in the brain remains elusive. We report here that the developmentally programmed FMRP expression represses the translation of microtubule associated protein 1B (MAP1B) and is required for the accelerated decline of MAP1B during active synaptogenesis in neonatal brain development. The lack of FMRP results in misregulated MAP1B translation and delayed MAP1B decline in the Fmr1 KO brain. Furthermore, the aberrantly elevated MAP1B protein expression leads to abnormally increased microtubule stability in Fmr1 KO neurons. Together, these results indicate that FMRP plays critical roles in controlling cytoskeleton organization during neuronal development, and the abnormal microtubule dynamics is a conceivable underlying factor for the pathogenesis of fragile X mental retardation.T he absence of fragile X mental retardation protein (FMRP), a messenger ribonucleoprotein (mRNP) associated with a subclass of brain mRNAs, results in fragile X mental retardation, affecting 1 in 4,000 males and 1 in 8,000 females (1-3). The lack of FMRP results in delayed dendritic spine maturation in fragile X patients as well as in Fmr1 knockout (KO) mice (4-8), indicating the essential role of FMRP in synapse development. Furthermore, the association of FMRP with translating polyribosomes (9-12) and micro-RNA machinery (13) suggests that FMRP governs translation efficiency of its mRNA targets, which in turn modulates synaptic development and plasticity.FMRP has been shown to act as a translation repressor for its associated mRNAs in vitro as well as in cultured cell lines (14-17). To date, Ͼ400 mRNAs have been identified to associate with FMRP in vivo (18-21). In fragile X patient cells and synaptoneurosomes isolated from the Fmr1 KO brain, the lack of FMRP causes abnormal polyribosome-association of several mRNAs that normally bind to FMRP (18,21). Consistent with the proposed function of FMRP in regulating translation in synaptic plasticity, activity-dependent production of the synaptic protein PSD95 is abrogated in the Fmr1 KO primary neuronal cultures (22). In addition, the mRNA of the microtubuleassociated protein 1B (MAP1B), a neuronal MAP playing principle roles in neurite and synapse development (23), is a predicted target of FMRP (18,19,21). Interestingly, deficiency of Drosophila Fmr1 (dFmr1) results in abnormally elevated expression of the microtubule associated protein Futsch and synaptic over growth at the neuromuscular...

show abstract

Section: Discussionmentioning

confidence: 93%

The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development

Wang

Liang

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

288

266

View full text Add to dashboard Cite

show abstract

“…Polyclonal GFP antibody was raised against glutathione S-transferase-tagged GFP and affinity purified (Cristea et al, 2005). Rabbit polyclonal MAP1B antibody NR (1:1000) were gifts from Dr. Fischer (Medical College of Pennsylvania Hahnemann University, Philadelphia, PA) (Fischer and Romano-Clarke, 1990;Ma et al, 1999). Anti-c-myc agarose affinity gel was purchased from Sigma.…”

Section: Methodsmentioning

confidence: 99%

Induction of Autophagy in Axonal Dystrophy and Degeneration

et al. 2006

View full text Add to dashboard Cite

Autophagy is a highly regulated cellular mechanism for the bulk degradation of cytoplasmic contents. It has been implicated in a variety of physiological and pathological conditions relevant to neurological diseases. However, the regulation of autophagy in neurons and its role in neuronal and axonal pathology are not yet understood. Using transgenic mice producing green fluorescent protein-tagged autophagic marker microtubule-associated protein light chain 3 (GFP-LC3), we provide molecular evidence for the induction of autophagy in axonal dystrophy and degeneration in Purkinje cells of the Lurcher mice, a model for excitotoxic neurodegeneration. We show that the excitotoxic insult of Lurcher mutation triggers an early response of Purkinje cells involving accumulation of GFP-LC3-labeled autophagosomes in axonal dystrophic swellings (a hallmark of CNS axonopathy). In brain, LC3 interacts with high affinity with the microtubule-associated protein 1B (MAP1B). We show that MAP1B binds to LC3 of both cytosolic form (LC3I) and lipidated form (LC3II).Moreover, in cell culture, overexpression of MAP1B results in reduced LC3II levels and number of GFP-LC3-labeled autophagosomes; phosphorylated MAP1B is associated with GFP-LC3-labeled autophagosomes. Furthermore, in brain, phosphorylated MAP1B accumulates in axonal dystrophic swellings of degenerating Purkinje cells and binds to LC3 at increased level. Therefore, the MAP1B-LC3 interaction may participate in regulation of LC3-associated autophagosomes in neurons, in particular at axons, under normal and pathogenic conditions. We propose that induction of autophagy serves as an early stress response in axonal dystrophy and may participate in the remodeling of axon structures.

show abstract

Section: Introductionmentioning

confidence: 99%

“…MAP1B expression is markedly upregulated during neurite outgrowth in various types of neurons (Gordon-Weeks and Fischer, 2000), and MAP1B knockout mice exhibit a range of abnormalities in axonal extension and path finding (Meixner et al, 2000;Gonzalez-Billault et al, 2001;Bouquet et al, 2004). More recent studies indicated that MAP1B expression is not restricted in neurons, but also is detected in oligodendrocytes and Schwann cells that produce myelin in the central and peripheral nervous system (CNS and PNS), respectively (Fischer et al, 1990;Ma et al, 1999). In particular, MAP1B expression is elevated in oligodendrocytes that initiate ensheathment of neuronal axons during normal brain development (Wu et al, 2001) as well as in Schwann cells during nerve regeneration (Ma et al, 1999).…”

mentioning

confidence: 99%

“…More recent studies indicated that MAP1B expression is not restricted in neurons, but also is detected in oligodendrocytes and Schwann cells that produce myelin in the central and peripheral nervous system (CNS and PNS), respectively (Fischer et al, 1990;Ma et al, 1999). In particular, MAP1B expression is elevated in oligodendrocytes that initiate ensheathment of neuronal axons during normal brain development (Wu et al, 2001) as well as in Schwann cells during nerve regeneration (Ma et al, 1999).The functional importance of MAP1B in CNS myelination is further reinforced by the defects of myelin development in the MAP1B knockout mice (Meixner et al, 2000).Despite the important function of MAP1B in the development and function of the nervous system, molecular mechanisms that promote MAP1B expression in neurons remain poorly understood and have not been investigated in oligodendrocytes. In neurons, a coordinated action of several transcription factors are thought to control MAP1B gene transcription (Montesinos et al, 2001;Foucher et al, 2003), which up-regulates MAP1B expression during neuronal differentiation.…”

mentioning

confidence: 99%

See 1 more Smart Citation

QKI Binds MAP1B mRNA and Enhances MAP1B Expression during Oligodendrocyte Development

Zhao

Chen

et al. 2006

MBoC

View full text Add to dashboard Cite

Microtubule-associated protein 1B (MAP1B) is essential for neural development. Besides the abundant expression in neurons, MAP1B recently was found in myelinating oligodendroglia. Moreover, MAP1B deficiency causes delayed myelin development, suggesting the functional importance of MAP1B in oligodendroglia. However, molecular mechanisms that control MAP1B expression in oligodendroglia remain elusive. We report here that MAP1B mRNA is markedly upregulated in the oligodendroglia cell line CG4 upon induced differentiation, leading to elevated MAP1B protein production. A coordinated regulation of homeoprotein transcription factors was observed during CG4 cell differentiation, which recapitulates the regulation in neurons that promotes MAP1B transcription. Hence, transcriptional regulation of MAP1B appears to be a common mechanism in both neurons and oligodendroglia. In addition, we found posttranscriptional regulation of MAP1B mRNA by the selective RNA-binding protein QKI in oligodendroglia. The 3UTR of MAP1B mRNA interacts with QKI, and oligodendroglia-specific QKI-deficiency in the quakingviable mutant mice resulted in reduced MAP1B mRNA expression. Moreover, RNAi-mediated QKI-knockdown caused destabilization of the MAP1B mRNA in CG4 cells. Furthermore, forced expression of exogenous QKI was sufficient for promoting MAP1B expression. Because QKI is absent in neurons, QKI-dependent stabilization of MAP1B mRNA provides a novel mechanism for advancing MAP1B expression specifically in oligodendroglia during brain development. INTRODUCTIONMicrotubule-associated proteins (MAPs) control the dynamic organization of microtubule cytoskeleton, which in turn governs normal cell growth and development (Takemura et al., 1992;Hirokawa, 1994). Among these MAPs, MAP1B is predominantly expressed in the nervous system and is the earliest MAP detected in the embryonic brain (Tucker et al., 1989;Ma et al., 1997;Ohyu et al., 1997). Historically, MAP1B, which has been studied mainly in the developing neurons, plays essential roles in neurite outgrowth, axonal extension, and path finding (Gonzalez-Billault et al., 2001, 2002Bouquet et al., 2004). MAP1B expression is markedly upregulated during neurite outgrowth in various types of neurons (Gordon-Weeks and Fischer, 2000), and MAP1B knockout mice exhibit a range of abnormalities in axonal extension and path finding (Meixner et al., 2000;Gonzalez-Billault et al., 2001;Bouquet et al., 2004). More recent studies indicated that MAP1B expression is not restricted in neurons, but also is detected in oligodendrocytes and Schwann cells that produce myelin in the central and peripheral nervous system (CNS and PNS), respectively (Fischer et al., 1990;Ma et al., 1999). In particular, MAP1B expression is elevated in oligodendrocytes that initiate ensheathment of neuronal axons during normal brain development (Wu et al., 2001) as well as in Schwann cells during nerve regeneration (Ma et al., 1999).The functional importance of MAP1B in CNS myelination is further reinforced by the defects of myelin devel...

show abstract

Induction of microtubule-associated protein 1B expression in Schwann cells during nerve regeneration

Cited by 33 publications

References 62 publications

The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development

The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development

Induction of Autophagy in Axonal Dystrophy and Degeneration

QKI Binds MAP1B mRNA and Enhances MAP1B Expression during Oligodendrocyte Development

Contact Info

Product

Resources

About