Motor protein-based active transport is essential for mRNA localization and local translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased yeast two–hybrid screen for interactions between murine RNA-binding proteins (RBPs) and motor proteins, here we identified protein interaction with APP tail-1 (PAT1) as a potential direct adapter between zipcode-binding protein 1 (ZBP1, a β-actin RBP) and the kinesin-I motor complex. The amino acid sequence of mouse PAT1 is similar to that of the kinesin light chain (KLC), and we found that PAT1 binds to KLC directly. Studying PAT1 in mouse primary hippocampal neuronal cultures from both sexes and using structured illumination microscopic imaging of these neurons, we observed that brain-derived neurotrophic factor (BDNF) enhances co-localization of dendritic ZBP1 and PAT1 within granules that also contain kinesin-I. PAT1 is essential for BDNF-stimulated neuronal growth cone development and dendritic protrusion formation, and we noted that ZBP1 and PAT1 co-locate along with β-actin mRNA in actively transported granules in living neurons. Acute disruption of the PAT1–ZBP1 interaction in neurons with PAT1 siRNA or a dominant-negative ZBP1 construct diminished localization of β-actin mRNA but not of Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) mRNA in dendrites. The aberrant β-actin mRNA localization resulted in abnormal dendritic protrusions and growth cone dynamics. These results suggest a critical role for PAT1 in BDNF-induced β-actin mRNA transport during postnatal development and reveal a new molecular mechanism for mRNA localization in vertebrates.

The etiology of Posner-Schlossman syndrome (PSS) remains unknown. The association of human leukocyte antigens (HLA) allelic diversity with PSS has been poorly investigated. To evaluate the association of allelic polymorphisms of class I HLA-A, -B and -C and class II HLA-DRB1 and -DQB1 with PSS, 100 unrelated patients with PSS and 128 age- and ethnically matched control subjects were recruited from a southern Chinese Han population. Polymorphisms in exons 2–4 for HLA-A, -B, -C loci, exon 2 for HLA-DRB1 and exons 2,3 for HLA-DQB1 were analyzed for association with PSS at allele and haplotype levels. The allele frequency of HLA-C*1402 in PSS patients was significantly higher than that in controls (P = 0.002, OR = 4.12). This association survived the Bonferroni correction (Pc = 0.04). The allele frequency of HLA-B*1301 in PSS patients was lower than that in the control group (P = 0.003, OR = 0.21), although this association did not survive the Bonferroni correction (Pc = 0.16). In PSS patients, the haplotype frequencies of HLA-A*1101~C*1402 and B*5101~C*1402 were higher than that in controls (P = 0.03, OR = 4.44; P = 0.02, OR = 3.20; respectively), while the HLA-B*1301~C*0304 was lower than that in controls (P = 0.007, OR = 0.23), although these associations did not survive the Bonferroni correction (Pc > 0.16). This study for the first time demonstrated that polymorphisms at the HLA-B and HLA-C loci were nominally associated with PSS in the southern Chinese Han population. Our results suggest that HLA-C*1402, A*1101~C*1402 and B*5101~C*1402 might be risk factors for PSS, whereas HLA-B*1301 plus B*1301~C*0304 might be protective factors against PSS, but even larger datasets are required to confirm these findings. Findings from this study provide valuable new clues for investigating the mechanisms and development of new diagnosis and treatment for PSS.

Posner-Schlossman syndrome (PSS) shares some clinical features with uveitis and open angle glaucoma. Cytokines and autoantibodies have been associated with uveitis and open angle glaucoma. However, the role of serum cytokines and autoantibodies in the pathogenesis of PSS remains unknown. This study aimed to evaluate the associations of type 1 T helper (Th1) and Th17 related cytokines and autoantibodies with PSS. Peripheral blood serum samples were collected from 81 patients with PSS and 97 gender- and age-matched healthy blood donors. Th1 and Th17 related cytokines, including interleukin-1β (IL-1β), IL-12, tumor necrosis factor-α (TNF-α), interferon- γ (IFN-γ), IL-6 and IL-17, and glucose-6-phosphate isomerase (GPI) were determined by double antibody sandwich ELISA. Anti-nuclear antibody (ANA), anti-keratin antibody (AKA) and anti-neutrophil cytoplasmic antibody (ANCA) were detected by indirect immunofluorescence assay. Anti-cardiolipin antibody (ACA)-IgG, ACA-IgM, ACA-IgA, anti-double stranded DNA (anti-dsDNA) and anti-cyclic citrullinated peptide antibody (anti-CCP) were detected by indirect ELISA. Serum levels of IL-1β, IL-12 and IL-6 in PSS patients were significantly lower than those in controls (P < 0.003), and these associations survived the Bonferroni correction (Pc < 0.018). There was no significant difference in serum levels of TNF-α, IFN-γ and IL-17 between the PSS and control groups (Pc > 0.12). Positive rate of serum anti-dsDNA in PSS patients was significantly higher than that in the control group (P = 0.002, Pc = 0.018), while positive rates of serum ANA, AKA, ANCA, ACA-IgG, ACA-IgM, ACA-IgA, GPI and anti-CCP in the PSS group were not significantly different from those in the control group (Pc > 0.09). These results suggest that anti-dsDNA may contribute to the pathogenesis of PSS, while Th1 and Th17 related cytokines and other autoantibodies may not be major contributors to PSS.

Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) are well-known key immune checkpoints that play a crucial dampening effect on regulating T-cell homeostasis and self-tolerance. In this study, we aimed to evaluate the association between immune checkpoints (CTLA-4 and PD-1) and Posner-Schlossman syndrome (PSS) in a southern Chinese population. A total of 137 patients with PSS and 139 healthy controls from a southern Chinese population were recruited. Five single nucleotide polymorphisms (SNPs) of CTLA-4 (rs733618, rs4553808, rs5742909, rs231775, and rs3087243) and five SNPs of PD-1 (rs10204525, rs2227981, rs2227982, rs41386349, and rs36084323) were genotyped by SNaPshot technique. Soluble CTLA-4 (sCTLA-4) and soluble PD-1 (sPD-1) were determined by ELISA and antibody array assay, respectively. The frequencies of T allele at rs733618 and A allele at rs231775 of CTLA-4 were significantly higher in PSS patients than in healthy controls (corrected p (Pc) = 0.037; Pc = 0.044, respectively). The haplotype frequencies of CACGG haplotype (rs733618-rs4553808-rs5742909-rs231775-rs3087243) of CTLA-4 and TGAGC haplotype (rs10204525-rs2227981-rs2227982-rs41386349-rs36084323) of PD-1 in the PSS group was significantly lower than those in the control group (Pc = 0.015, p = 0.034, respectively). Circulating plasma levels of sCTLA-4 and sPD-1 in PSS patients were significantly higher than those in controls (all p &lt; 0.001). The present study suggests that CTLA-4 and PD-1 genetic polymorphisms are associated with the susceptibility to PSS in a southern Chinese population. The upregulated circulating plasma protein levels of sCTLA-4 and sPD-1 might provide some hints regarding the dysfunction of immune checkpoints in PSS during the active status.