Ratiometric measurement of MAM Ca dynamics using a modified CalfluxVTN.

Mitochondria-associated ER membrane (MAM) is a structure where these calcium-regulating organelles form close physical contact sites for efficient Ca crosstalk. Despite the central importance of MAM Ca dynamics in diverse biological processes, directly and specifically measuring Ca concentrations inside MAM is technically challenging. Here, we develop MAM-Calflux, a MAM-specific BRET-based Ca indicator.

Schizophrenia-associated dysbindin modulates axonal mitochondrial movement in cooperation with p150.

Mitochondrial movement in neurons is finely regulated to meet the local demand for energy and calcium buffering. Elaborate transport machinery including motor complexes is required to deliver and localize mitochondria to appropriate positions. Defects in mitochondrial transport are associated with various neurological disorders without a detailed mechanistic information.

Dopamine D1 Receptor (D1R) Expression Is Controlled by a Transcriptional Repressor Complex Containing DISC1.

Disrupted-in-Schizophrenia 1 (DISC1) is a scaffold protein implicated in various psychiatric diseases. Dysregulation of the dopamine system has been associated with DISC1 deficiency, while the molecular mechanism is unclear. In this study, we propose a novel molecular mechanism underlying the transcriptional regulation of the dopamine D1 receptor (D1R) in the striatum via DISC1.

DISC1 Modulates Neuronal Stress Responses by Gate-Keeping ER-Mitochondria Ca Transfer through the MAM.

A wide range of Ca-mediated functions are enabled by the dynamic properties of Ca, all of which are dependent on the endoplasmic reticulum (ER) and mitochondria. Disrupted-in-schizophrenia 1 (DISC1) is a scaffold protein that is involved in the function of intracellular organelles and is linked to cognitive and emotional deficits. Here, we demonstrate that DISC1 localizes to the mitochondria-associated ER membrane (MAM).

Functional expression of dopamine D2 receptor is regulated by tetraspanin 7-mediated postendocytic trafficking.

The dopaminergic system plays an essential role in various functions of the brain, including locomotion, memory, and reward, and the deregulation of dopaminergic signaling as a result of altered functionality of dopamine D2 receptor (DRD2) is implicated in multiple neurologic and psychiatric disorders. Tetraspanin-7 (TSPAN7) is expressed to variable degrees in different tissues, with the highest level in the brain, and multiple mutations in TSPAN7 have been implicated in intellectual disability. Here, we tested the hypothesis that TSPAN7 may be a binding partner of DRD2 that is involved in the regulation of its functional activity.

Regulation of the actin cytoskeleton by the Ndel1-Tara complex is critical for cell migration.

Nuclear distribution element-like 1 (Ndel1) plays pivotal roles in diverse biological processes and is implicated in the pathogenesis of multiple neurodevelopmental disorders. Ndel1 function by regulating microtubules and intermediate filaments; however, its functional link with the actin cytoskeleton is largely unknown. Here, we show that Ndel1 interacts with TRIO-associated repeat on actin (Tara), an actin-bundling protein, to regulate cell movement.

Disrupted-in-schizophrenia 1 (DISC1) and Syntaphilin collaborate to modulate axonal mitochondrial anchoring.

In neuronal axons, the ratio of motile-to-stationary mitochondria is tightly regulated by neuronal activation, thereby meeting the need for local calcium buffering and maintaining the ATP supply. However, the molecular players and detailed regulatory mechanisms behind neuronal mitochondrial movement are not completely understood. Here, we found that neuronal activation-induced mitochondrial anchoring is regulated by Disrupted-in-schizophrenia 1 (DISC1), which is accomplished by functional association with Syntaphilin (SNPH).