Geon The Role of Actin Dynamics in Schizophrenia

 

Abstract

A growing body of evidence suggests that actin dynamics is implicated in schizophrenia (SCZ). This paper explains how actin dynamics regulates the occlusion of GluN2B-NMDARs by the CABT complex, which could underlie the NMDAR hypofunction in SCZ (Paper 25). In the spine, CABT may bind either F-actin or GluN2B. Binding of CABT to F-actin would not block NMDAR currents. However, if F-actin is depolymerized, CABT would be forced to bind and occlude the GluN2B-containing NMDARs. The Shank3 deficiency could promote F-actin depolymerization by enhancing cofilin activity, thereby facilitating the CABT-GluN2B binding. Arc plays a critical role in the stabilization of F-actin by counteracting cofilin. Its deficiency also facilitates the CABT-GluN2B binding. CDC42 is an upstream regulator of cofilin. Its mRNA is reduced in SCZ. This finding was proposed to account for the decreased dendritic spine density in SCZ. However, the protein level of CDC42 was unchanged in SCZ. A study demonstrates that loss of GluN2B-NMDARs reduces dendritic spine density. Therefore, the dendritic spine deficits in SCZ could arise from the CABT occlusion of GluN2B-NMDARs.

 

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