Li KK, etal., PLoS One. 2015 May 26;10(5):e0127910. doi: 10.1371/journal.pone.0127910. eCollection 2015.
Many facets of the tumor biology of medulloblastoma (MB) have not been fully elucidated. Collapsin response mediator protein 1 (CRMP1) is a member of cytoplasmic family of proteins that regulate the development of central nervous system. Recent studies demonstra
ted that CRMP1 could function as an invasion suppressor. We reported previously that high mobility group AT-hook 1 (HMGA1) contributed to development of MB and regulated its growth and migration/invasion. Transcriptional profiling and quantitative RT-PCR revealed increased expression of CRMP1 in HMGA1-depleted cells, suggesting that CRMP1 may be a downstream target of HMGA1 in MB. In this study, we showed HMGA1 can bind CRMP1 promoter by chromatin immunoprecipitation (ChIP) assay. Luciferase assay demonstrated a marked enhancement of CRMP1 transcription activity in HMGA1-depleted cells. Furthermore, quantitative RT-PCR revealed a negative correlation between HMGA1 and CRMP1 in 32 MB samples. To investigate the biological roles of CRMP1 in MB pathogenesis, we established MB clones stably expressing CRMP1. Functional analysis revealed that expression of CRMP1 significantly inhibited proliferation, migration, invasion and formation of filopodia and intense stress fiber of MB cells. Our data suggest that HMGA1 regulates CRMP1 expression and CRMP1 is implicated in MB pathogenesis.
Nakamura F, etal., Nat Commun. 2014 Oct 31;5:5325. doi: 10.1038/ncomms6325.
Reorganization of the actin cytoskeleton is an early cellular response to various extracellular signals. Sema3A, a repulsive axon guidance molecule, induces the reorganization of actin cytoskeleton in the growth cones. Collapsin response mediator protein 1 (CRMP1
>) mediates the intracellular Sema3A signalling through its Ser522 phosphorylation. Here we show that UNC-33, CRMP1 C. elegans homologue, interacts with FLN-1, an actin-binding Filamin-A orthologue. In nematodes, this interaction participates in the projection of DD/VD motor neurons. CRMP1 binds both the actin-binding domain and the last immunoglobulin-like repeat of Filamin-A. The alanine mutants of Filamin-A or CRMP1 in their interacting residues suppress the Sema3A repulsion in neurons. Conversely, a phosphor-mimicking mutant CRMP1(Ser522Asp) enhances the Sema3A response. Atomic-force microscopy analysis reveals that the V-shaped Filamin-A changes to a condensed form with CRMP1(Ser522Asp). CRMP1(Ser522Asp) weakens the F-actin gelation crosslinked by Filamin-A. Thus, phosphorylated CRMP1 may remove Filamin-A from the actin cytoskeleton to facilitate its remodelling.
Yao L, etal., Mol Neurobiol. 2016 Mar;53(2):879-93. doi: 10.1007/s12035-014-9049-2. Epub 2014 Dec 20.
CRMP1, a member of the collapsin response mediator protein family (CRMPs), was reported to regulate axon outgrowth in Sema3A signaling pathways via interactions with its co-receptor protein neuropilin-1 and plexin-As through the Fyn-cyclin-dependent kinase 5 (CD
K5) cascade and the sequential phosphorylation of CRMP1 by lycogen synthase kinase-3beta (GSK-3beta). Using yeast two-hybrid, we identified a new molecule, Speedy A1 (Spy1), a member of the Speedy/RINGO family, with an interaction with CRMP1. Besides, for the first time, we observed the association of CRMP1 with actin. Based on this, we wondered the association of them and their function in Sema3A-induced growth cones collapse and regeneration process after SNC. During our study, we constructed overexpression plasmid and short hairpin RNA (shRNA) to question the relationship of CRMP1/Spy1 and CRMP1/actin. We observed the interactions of CRMP1/Spy1 and CRMP1/actin. Besides, we found that Spy1 could affect CRMP1 phosphorylation actived by CDK5 and that enhanced CRMP1 phosphorylation might disturb the combination of CRMP1 and actin, which would contribute to abnormal of Sema3A-induced growth cones collapse and finally lead to influent regeneration process after rat sciatic nerve crush. Through rat walk footprint test, we also observed the variance during regeneration progress, respectively. We speculated that CRMP1 interacted with Spy1 which would disturb the association of CRMP1 with actin and was involved in the collapse of growth cones induced by Sema3A and regeneration after sciatic nerve crush.
