Disease relevance of Dpysl3

• CRMP-4 was abundant in the cytosol of B35 neuroblastoma cells and its concentration was measured as approximately 1.7 microM [1].
• Calpain-mediated truncation of dihydropyrimidinase-like 3 protein (DPYSL3) in response to NMDA and H2O2 toxicity [2].
• Two weeks after ischemia, over 60% of these cells became young neurons as determined by colabeling with BrdU and a cytoplasmic protein (CRMP-4) involved in axonal guidance during development [3].
• Induction of CRMP-4 in striatum of adult rat after transient brain ischemia [4].

High impact information on Dpysl3

• However, the growth cone collapse-inducing protein Sema3A increases Cdk5 activity and promotes phosphorylation of CRMP2 (but not CRMP4) [5].
• Here, we report that a monoclonal antibody against chondroitin sulfate-binding proteins from neonatal rat brain recognizes collapsin response mediator protein-4 (CRMP-4), which belongs to a family of proteins involved in collapsin/semaphorin 3A signaling [6].
• Overexpression of CRMP-4 inhibited the migration of B35 neuroblastoma cells, while knockdown of CRMP-4 enhanced cell migration and disturbed rib-like actin-structures in lamellipodia [1].
• These findings suggest a specific regulatory role of CRMP-4 towards the actin cytoskeleton which may by be relevant for growth cone collapse [1].
• In primary cortical cultures, glutamate (NMDA) excitotoxicity and oxidative stress (H2O2) caused the cleavage of DPYSL3, resulting in the appearance of a doublet of 62 kDa and 60 kDa [2].

Biological context of Dpysl3

• Furthermore, whereas TUC-4a is expressed throughout life, TUC-4b is expressed exclusively during embryonic development [7].

Anatomical context of Dpysl3

• Here, we show that CRMP-4 co-localizes with F-actin in regular rib-like structures within lamellipodia of B35 neuroblastoma cells [1].
• From DRP 3 onwards, CNTFRalpha mRNA appeared in photoreceptor cells located in the outer part of the outer nuclear layer [8].
• The functional relevance of this N-terminal domain is demonstrated by the finding that overexpression of TUC-4b, but not TUC-4a, results in increased neurite length and branching [7].
• TUC-4b is localized to SV2 (synaptic vesicle protein 2)-positive vesicles in the central domain of the growth cone, suggesting a potential role in growth cone vesicle transport [7].
• RESULTS: CRMP-4, a marker of immature neuron, could be expressed in the ipsilateral striatum and cerebral cortex at 1st and 2nd week after the ischemia-reperfusion; nestin, a marker of neural stem cell, occurred in above regions from several hours to 2 weeks [4].

Associations of Dpysl3 with chemical compounds

• CRMP-4 costained with nestin and with BrdU incorporation [4].

Other interactions of Dpysl3

• Collectively, these studies demonstrate for the first time that DPYSL3 is a calpain substrate [2].
• Significant higher CRMP-2 protein but not CRMP-4 protein was found in the hypothyroid rats [9].
• Furthermore, TUC-4b interacts with the SH3A (Src homology 3A) domain of intersectin, an endocytic-exocytic adaptor protein [7].

Analytical, diagnostic and therapeutic context of Dpysl3

• The co-localization of CRMP-4 and nestin or BrdU was analyzed by double staining combined with confocal laser scanning microscopy [4].

References