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Arginine methylation is a common post-translational modification that modulates protein function. SCY1 like pseudokinase 1 (SCYL1) is crucial for neuronal functions and interacts with γ2-COP to form coat protein complex I (COPI) vesicles that regulate Golgi morphology. However, the molecular mechanism by which SCYL1 is regulated remains unclear. Here, we report that the γ2-COP-binding site of SCYL1 is arginine-methylated by protein arginine methyltransferase 1 (PRMT1), and that SCYL1 arginine methylation is important for the interaction of SCYL1 with γ2-COP. PRMT1 was colocalized with SCYL1 in Golgi fraction. Inhibition of PRMT1 suppressed axon outgrowth and dendrite complexity via abnormal Golgi morphology. Knockdown of SCYL1 by small interfering RNA (siRNA) inhibited axon outgrowth, and the inhibitory effect was rescued by siRNA-resistant SCYL1, but not SCYL1 mutant, in which the arginine methylation site was replaced. Thus, PRMT1 regulates Golgi morphogenesis via SCYL1 arginine methylation. We propose that SCYL1 arginine methylation by PRMT1 contributes to axon and dendrite morphogenesis in neurons.

Inflammatory macrophages play a fundamental role in neuropathic pain. In this study, we demonstrate the effects of peripheral interleukin-13 (IL-13) on neuropathic pain after partial sciatic nerve (SCN) ligation (PSL) in mice. IL-13 receptor α1 was upregulated in accumulating macrophages in the injured SCN after PSL. Treatment with IL-13 reduced inflammatory macrophage-dominant molecules and increased suppressive macrophage-dominant molecules in cultured lipopolysaccharide-stimulated peritoneal macrophages and ex vivoSCN subjected to PSL. Moreover, the perineural administration of IL-13 relieved tactile allodynia after PSL. These results suggest that IL-13 reverses inflammatory macrophage-dependent neuropathic pain viaa phenotype shift toward suppressive macrophages.

DisruptedinSchizophrenia 1 DISC1 and its molecular cascade have been implicated in the pathophysiology of major psychoses. Previously, we identified pericentrin 2 PCNT2 and DISC1binding zinc finger protein DBZ as binding partners of DISC1; further, we observed elevated expression of PCNT2in the postmortem brains and in the lymphocytes of bipolar disorder patients, compared to controls. Here, we examined the association of PCNT2with schizophrenia in a case–control study of Japanese cohorts. We also examined the association of DBZwith schizophrenia and with bipolar disorder, and compared the mRNA levels of DBZin the postmortem brains of schizophrenia, bipolar and control samples. DNA from 180 schizophrenia patients 201 controls were used for the association study of PCNT2and DBZwith schizophrenia. Association of DBZwith bipolar disorder was examined in DNA from 238 bipolar patients and 240 age and gendermatched controls. We observed significant allelic and genotypic associations of the PCNT2SNPs, rs2249057, rs2268524, and rs2073380 SerArg with schizophrenia; the association of rs2249057 P  0.002 withstand multiple testing correction. Several two SNP and three SNPhaplotypes showed significant associations; the associations of haplotypes involving rs2249057 withstand multiple testing correction. No associations were observed for DBZwith schizophrenia or with bipolar disorder; further, there was no significant difference between the DBZmRNA levels of control, schizophrenia and bipolar postmortem brains. We suggest a possible role of PCNT2 in the pathogenesis of schizophrenia. Abnormalities of PCNT2, the centrosomal protein essential for microtubule organization, may be suggested to lead to neurodevelopmental abnormalities. © 2009 WileyLiss, Inc.

Background: Deficiency of pituitary adenylyl cyclase-activating polypeptide (PACAP) and its specific receptor, PAC1, causes a schizophrenia-like phenotype in mice. In addition, the relation of the PACAP and PAC1 genes to schizophrenia has been shown by single-nucleotide polymorphism association studies. Furthermore, PACAP is reported to be involved in the function of disrupted-in-schizophrenia 1. Objective: To summarize briefly the recent evidence relating the PACAP system and schizophrenia and discuss the application of PACAP to the treatment of schizophrenia. Results/conclusion: The regulation of PACAPergic signals is an interesting potential treatment for schizophrenia. Further studies of PACAP signals and the association of PACAP signals with schizophrenia should shed the light on the utility of this approach in the treatment of schizophrenia.

The human ADP-ribosylation factor-like protein, ARF4L is a member of the ARF family, which are small GTP-binding proteins that play significant roles in vesicle transport and protein secretion. However, little is known about the physiological roles of ARF4L. In this study, to understand the biological functions of ARF4L, we carried out immunocytochemical analysis of ARF4L molecules with mutations in the functional domains. ARF4L was shown to be distributed to the plasma membrane following binding to GTP (Q80L), and into endosomes following binding to GDP (T35N). Moreover, the inactive-form of ARF4L (T35N) causes localization of transferrin receptors to the endosomal compartment, while the active form (Q80L) causes transport to the plasma membrane. These findings indicate that ARF4L drive the transport of cargo protein and subsequent fusion of recycling vesicles with the plasma membrane for maintenance of the cell surface.