Schizophrenia is a severe chronic mental disorder with a high genetic component in its etiology. Several lines of study have suggested that synaptic dysfunction may underlie the pathogenesis of schizophrenia. Neuroligin proteins function as cell-adhesion molecules at post-synaptic membrane and play critical roles in synaptogenesis and synaptic maturation. In this study, we systemically sequenced all the exons and promoter region of neuroligin-2 (NLGN2) gene in a sample of 584 schizophrenia patients and 549 control subjects from Taiwan. In total, we identified 19 genetic variants, including six rare missense mutations such as R215H (one patient), V510M (two patients), R621H (one patient), A637T (two patients), P800L (one patient and one control) and A819S (one patient and one control). In silico analysis predicted that two patient-specific missense mutations, R215H and R621H, had damaging effect, whereas the other missense mutations were benign. Importantly, functional analysis with immunocytochemistry and electrophysiological recordings identified the R215H mutant as a loss-of-function mutant in inducing GABAergic synaptogenesis. Mechanistically, the synaptogenic deficiency of R215H mutant was due to its retention inside the endoplasmic reticulum and inability to be transported to cell membrane. Our study suggests that defects in GABAergic synapse formation in the brain may be an important contributing factor for the onset of schizophrenia. In the family study of this mutation, we found his elder brother also carried this mutation but did not have psychiatric symptoms, indicating that this mutation has incomplete penetrance, and thus the clinical relevance of this mutation should be interpreted with caution.

BackgroundThe whitefly, Bemisia tabaci (Hemiptera: Aleyrodidae), is one of the most widely distributed agricultural pests. In recent years, B. tabaci Q has invaded China, and Q has displaced B in many areas now. In a number of regions of the world, invasion by B and/or Q has been followed by outbreaks of tomato yellow leaf curl virus (TYLCV). Our previous study showed TYLCV directly and indirectly modified the feeding behavior of B. tabaci in favor of Q rather than B.Methodology/Principal FindingsIn this study, we quantified the salicylic acid (SA) titers and relative gene expression of SA in tomato leaves that were infested with viruliferous or non-viruliferous B and Q. We also measured the impacts of exogenous SA on the performance of B and Q, including the effects on ovary development. SA titer was always higher in leaves that were infested with viruliferous B than with viruliferous Q, whereas the SA titer did not differ between leaves infested with non-viruliferous B and Q. The relative gene expression of SA signaling was increased by feeding of viruliferous B but was not increased by feeding of viruliferous Q. The life history traits of B and Q were adversely affected on SA-treated plants. On SA-treated plants, both B and Q had lower fecundity, shorter longevity, longer developmental time and lower survival rate than on untreated plants. Compared with whiteflies feeding on control plants, those feeding on SA-treated plants had fewer oocytes and slower ovary development. On SA-treated plants, viruliferous B had fewer oocytes than viruliferous Q.Conclusions/SignificanceThese results indicate that TYLCV tends to induce SA-regulated plant defense against B but SA-regulated plant defense against Q was reduced. In other words, Q may have a mutualistic relationship with TYLCV that results in the reduction of the plant's defense response.

Edited by F. Anne StephensonThe ␥2 subunit of GABA type A receptors (GABA A Rs) is thought to be subject to palmitoylation by both Golgi-associated DHHC-type zinc finger protein (GODZ; also known as DHHC3) and its paralog Sertoli cell gene with a zinc finger domain-␤ (SERZ-␤; DHHC7) based on overexpression of enzymes and substrates in heterologous cells. Here we have further investigated the substrate specificity of these enzymes by characterization of GODZ and SERZ-␤ knock-out (KO) mice as well as double KO (DKO) neurons. Palmitoylation of ␥2 and a second substrate, growth-associated protein of 43 kDa, that is independently implicated in trafficking of GABA A Rs was significantly reduced in brain of GODZ KO versus wild-type (WT) mice but unaltered in SERZ-␤ KO mice. Accumulation of GABA A Rs at synapses, GABAergic innervation, and synaptic function were reduced in GODZ KO and DKO neurons to a similar extent, indicating that SERZ-␤ does not contribute to palmitoylation or trafficking of GABA A Rs even in the absence of GODZ. Notably, these effects were seen only when mutant neurons were grown in competition with WT neurons, thereby mimicking conditions of shRNA-transfected neurons previously used to characterize GODZ. However, GABA-evoked whole-cell currents of DKO neurons and the GABA A R cell surface expression in DKO neurons and GODZ or SERZ-␤ KO brain slices were unaltered, indicating that GODZ-mediated palmitoylation selectively controls the pool of receptors at synapses. The different substrate specificities of GODZ and SERZ-␤ in vivo were correlated with their differential localization to cis-versus trans-Golgi compartment, a mechanism that was compromised by overexpression of GODZ.S-Palmitoylation is an important posttranslational modification that involves the addition of the 16-carbon fatty acid chain palmitate via a thioester bond to Cys residues (1). This modification in turn can alter a protein's conformational state, membrane association, and complex formation as well as its susceptibility to other posttranslational modifications (2-4). Global analyses of rat synaptosomal fractions led to the discovery of nearly 300 palmitoylated synaptosomal protein candidates that illustrate the particular importance of palmitoylation in regulating the function of neuronal synapses (5).In mammalian cells, the palmitoylation reaction is catalyzed principally by a super gene family of 23 palmitoyl acyltransferases containing a DHHC motif in a cysteine-rich domain (DHHC-CRD) 3 that are both essential for enzyme function (6 -10). The mechanisms that determine substrate specificity of PATs remain poorly understood, although some specificity is observed upon overexpression of substrates and PATs in heterologous cells. However, increasing evidence suggests that the substrate specificity of DHHC-type PATs in vivo is much more stringent than in vitro. For example, the postsynaptic density (PSD) protein of 95-kDa (PSD-95) can be palmitoylated in heterologous cells by at least five members of the DHHC family of PATs (11), w...

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