CHL1 promotes Sema3A‐induced growth cone collapse and neurite elaboration through a motif required for recruitment of ERM proteins to the plasma membrane

Schlatter, Monika C.; Buhusi, Mona; Wright, Amanda; Maness, Patricia F.

doi:10.1111/j.1471-4159.2007.05013.x

Cited by 54 publications

(55 citation statements)

References 49 publications

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“…In support of this notion, it is interesting to note that secreted CHL1 ectodomain acts as a potent stimulator of neurite outgrowth in vitro (50). Notably, CHL1 interacts with semaphorin 3A during neurite outgrowth and growth cone collapse (53,54). Intriguingly, soluble L1 converts Sema3A-induced axonal repulsion into attraction (55,56).…”

Section: Discussionmentioning

confidence: 83%

β-Site Amyloid Precursor Protein (APP)-cleaving Enzyme 1 (BACE1)-deficient Mice Exhibit a Close Homolog of L1 (CHL1) Loss-of-function Phenotype Involving Axon Guidance Defects

Hitt¹,

Riordan²,

Kukreja

et al. 2012

Journal of Biological Chemistry

137

151

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Background:Little is known about BACE1 functions. Results: BACE1 Ϫ/Ϫ mice have axon guidance defects similar to those of CHL1 Ϫ/Ϫ mice; CHL1 undergoes BACE1-dependent processing in vivo; CHL1 and BACE1 co-localize in terminals and growth cones. Conclusion: BACE1 deficiency produces a CHL1 loss-of-function phenotype. Significance: BACE1 inhibition may cause axon guidance defects, adding a note of caution to BACE1 inhibitor drug development.

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Section: Discussionmentioning

confidence: 83%

β-Site Amyloid Precursor Protein (APP)-cleaving Enzyme 1 (BACE1)-deficient Mice Exhibit a Close Homolog of L1 (CHL1) Loss-of-function Phenotype Involving Axon Guidance Defects

Hitt¹,

Riordan²,

Kukreja

et al. 2012

Journal of Biological Chemistry

137

151

View full text Add to dashboard Cite

show abstract

“…Recently, Schlatter et al (2007) showed that CHL1 recruits ezrin to the membrane, and that this recruitment contributes to Sema3A induced growth cone collapse. Our data demonstrate that the binding of ERM proteins to Factin is inhibited by Sema3A signaling.…”

Section: Discussionmentioning

confidence: 99%

Semaphorin 3A inhibits ERM protein phosphorylation in growth cone filopodia through inactivation of PI3K

Gallo

2008

Developmental Neurobiology

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Ezrin-radixin-moesin (ERM) proteins are involved in the linkage of membranes to theactin filament (F-actin) cytoskeleton. Phosphorylation of the C-terminus activates the F-actin binding domain of ERM proteins by preventing the action of an autoinhibitory domain. In this study, we investigated whether a growth cone collapsing signal, semaphorin 3A (Sema3A), alters the state of ERM C-terminus phosphorylation. In the growth cones of dorsal root ganglion axons, phosphorylated ERM proteins localize to filopodia. We report that Sema3A inhibits ERM protein phosphorylation in growth cone filopodia. Significantly, Sema3A decreased ERM phosphorylation prior to the onset of growth cone collapse. Over-expression of the F-actin binding fragment of ERM proteins, which competes with endogenous ERM proteins for binding to F-actin, inhibited filopodial initiation and dynamics. Sema3A has been previously shown to inhibit phosphoinositide 3-kinase (PI3K) activity. Inhibition of PI3K resulted in the loss of phosphorylated ERM proteins from growth cone filopodia, and treatment with a PI3K activating peptide blocked the effects of Sema3A on ERM phosphorylation. Collectively, these observations demonstrate that inactivation of PI3K in response to Sema3A results in decreased phosphorylation of ERM proteins in filopodia thereby contributing to growth cone collapse.

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“…CHL1 has been shown to promote neurite outgrowth of cerebellar and hippocampal neurons, and suppress neuronal cell death. 68,69 In human, deletion or alteration of the CHL1 gene may contribute to mental defects associated with the 3p-syndrome, caused by distal deletions of the short (p) arm of chromosome 3, and schizophrenia. 20,70,71 CHL1-deficient mice have been shown to have aberrant connectivity of hippocampal mossy fibers and olfactory sensory axons, which resulted in behavior change secondary to the disruption of information processing.…”

Section: Synapse and Neurotransmissionmentioning

confidence: 99%

An integrated genomic analysis of gene-function correlation on schizophrenia susceptibility genes

Chu

Liu

2010

J Hum Genet

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Schizophrenia is a highly complex inheritable disease characterized by numerous genetic susceptibility elements, each contributing a modest increase in risk for the disease. Although numerous linkage or association studies have identified a large set of schizophrenia-associated loci, many are controversial. In addition, only a small portion of these loci overlaps with the large cumulative pool of genes that have shown changes of expression in schizophrenia. Here, we applied a genomic gene-function approach to identify susceptibility loci that show direct effect on gene expression, leading to functional abnormalities in schizophrenia. We carried out an integrated analysis by cross-examination of the literature-based susceptibility loci with the schizophrenia-associated expression gene list obtained from our previous microarray study (Journal of Human Genetics (2009) 54: 665-75) using bioinformatic tools, followed by confirmation of gene expression changes using qPCR. We found nine genes (CHGB, SLC18A2, SLC25A27, ESD, C4A/C4B, TCP1, CHL1 and CTNNA2) demonstrate gene-function correlation involving: synapse and neurotransmission; energy metabolism and defense mechanisms; and molecular chaperone and cytoskeleton. Our findings further support the roles of these genes in genetic influence and functional consequences on the development of schizophrenia. It is interesting to note that four of the nine genes are located on chromosome 6, suggesting a special chromosomal vulnerability in schizophrenia.

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CHL1 promotes Sema3A‐induced growth cone collapse and neurite elaboration through a motif required for recruitment of ERM proteins to the plasma membrane

Cited by 54 publications

References 49 publications

β-Site Amyloid Precursor Protein (APP)-cleaving Enzyme 1 (BACE1)-deficient Mice Exhibit a Close Homolog of L1 (CHL1) Loss-of-function Phenotype Involving Axon Guidance Defects

β-Site Amyloid Precursor Protein (APP)-cleaving Enzyme 1 (BACE1)-deficient Mice Exhibit a Close Homolog of L1 (CHL1) Loss-of-function Phenotype Involving Axon Guidance Defects

Semaphorin 3A inhibits ERM protein phosphorylation in growth cone filopodia through inactivation of PI3K

An integrated genomic analysis of gene-function correlation on schizophrenia susceptibility genes

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