Background: Dysbindin-1 isoforms are selectively reduced in schizophrenic brains. Results: Dysbindin-1C is required for the survival of hilar mossy cells and the maturation of adult newborn neurons in the dentate gyrus. Conclusion: Dysbindin-1C, but not -1A, regulates adult hippocampal neurogenesis in a non-cell autonomous manner. Significance: Reduced dysbindin-1C in the schizophrenic hippocampal formation likely contributes to the development of cognitive deficits.
Platelets respond to vascular injury via surface receptor stimulation and signaling events to trigger aggregation, procoagulant activation, and granule secretion during hemostasis, thrombosis, and vascular remodeling. Platelets contain three major types of secretory granules including dense granules (or δ-granules, DGs), α-granules (AGs), and lysosomes. The contents of platelet granules are specific. Platelet DGs store polyphosphate and small molecules such as ADP, ATP, Ca2+, and serotonin, while AGs package most of the proteins that platelets release. The platelet DGs and AGs are regarded as being budded from the endosomes and the trans-Golgi network (TGN), respectively, and then matured from multivesicular bodies (MVBs). However, the sorting machineries between DGs and AGs are different. Inherited platelet disorders are associated with deficiency of DGs and AGs, leading to bleeding diathesis in patients with Hermansky–Pudlak syndrome (HPS), gray platelet syndrome (GPS), and arthrogryposis, renal dysfunction, and cholestasis syndrome (ARC). Here, we reviewed the current understanding about how DGs differ from AGs in structure, biogenesis, and function. In particular, we focus on the sorting machineries that are involved in the formation of these two types of granules to provide insights into their diverse biological functions.
Hermansky-Pudlak syndrome (HPS) is a rare recessive disorder characterized by hypopigmentation, bleeding diathesis, and other symptoms due to multiple defects in lysosome-related organelles. Ten HPS subtypes have been identified with mutations in HPS1 to HPS10. Only four patients with HPS-1 have been reported in Chinese population. Using next-generation sequencing (NGS), we have screened 100 hypopigmentation genes and identified four HPS-1, two HPS-3, one HPS-5, and three HPS-6 in Chinese HPS patients with typical ocular or oculocutaneous albinism and the absence of platelet dense granules together with other variable phenotypes. All these patients except one homozygote were compound heterozygotes. Among these mutations, 14 were previously unreported alleles (four in HPS1, three in HPS3, two in HPS5, five in HPS6). Our results demonstrate the feasibility and utility of NGS-based panel diagnostics for HPS. Genotyping of HPS subtypes is a prerequisite for intervention of subtype-specific symptoms.
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