Geon A Novel Function of CRMP2:
Implication in Memory Extinction and Schizophrenia



Collapsin response mediator protein 2 (CRMP2) has a well-documented function: regulation of axonal and dendritic growth. Recently, it was found that in schizophrenia (SCZ) patients, the active (nonphosphorylated) CRMP2 is abnormally increased without sufficient phosphorylated CRMP2. This finding can be explained by the "CABT Hypothesis" originally proposed for memory extinction. The CABT Hypothesis posits that the CABT complex, consisting of a CRMP2 monomer, an alpha (α) and a beta (β) tubulin, may block the NMDA receptor (NMDAR), resulting in decreased NMDAR activity. Over the last two decades, extensive research has revealed that SCZ could be caused by the hypofunction of NMDARs. The blockade of a larger number of NMDARs by excess CABT complexes may underlie the NMDAR hypofunction in SCZ. Phosphorylated CRMP2 is known to disrupt its binding with the tubulin heterodimers, thereby reducing the number of CABT complexes. Hence, abundant total CRMP2 with low level of phosphorylated CRMP2 may increase CABT complexes, resulting in NMDAR hypofunction.


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