Calcium-dependent activator protein for secretion 2 interacts with the class II ARF small GTPases and regulates dense-core vesicle trafficking

The Ca(2+) -dependent activator protein for secretion (CAPS) family consists of two members (CAPS1 and CAPS2) and regulates the exocytosis of catecholamine-containing or neuropeptide-containing dense-core vesicles (DCVs) at secretion sites such as nerve terminals. A large fraction of CAPS1, however, is localized in the cell soma, and we have recently shown the possible involvement of somal CAPS1 in DCV trafficking in the trans-Golgi network. CAPS1 and CAPS2 are differentially expressed in various regions of the mouse brain but exhibit similar expression patterns in other tissues, such as the spleen. Thus, in the present study we analyzed whether CAPS2 displays similar subcellular localization and functional roles in the cell soma as CAPS1. We found that somal CAPS2 is associated with the Golgi membrane, and mediates binding and recruitment of the GDP-bound form of ARF4 and ARF5 (members of the membrane-trafficking small GTPase family) to the Golgi membrane. CAPS2 knockdown and overexpression of CAPS2-binding-deficient ARF4/ARF5 both induced accumulation of the DCV resident protein chromogranin?A around the Golgi apparatus. CAPS2 knockout mice have dilated trans-Golgi structures when viewed by electron microscopy. These results for CAPS2 strongly support our idea that the CAPS family proteins exert dual roles in DCV trafficking, mediating trafficking at both the secretion site for exocytosis and at the Golgi complex for biogenesis.     

Sequential expression of Efhc1/myoclonin1 in choroid plexus and ependymal cell cilia

EFHC1 is a gene mutated in patients with idiopathic epilepsies, and encodes the myoclonin1 protein. We here report the distribution of myoclonin1 in mouse. Immunohistochemical analyses revealed that the myoclonin1 first appeared at the roof of hindbrain at embryonic day 10 (E10), and moved on to choroid plexus at E14. At E18, it moved to ventricle walls and disappeared from choroid plexus. From neonatal to adult stages, myoclonin1 was concentrated in the cilia of ependymal cells at ventricle walls. At adult stages, myoclonin1 expression was also observed at tracheal epithelial cilia in lung and at sperm flagella in testis. Specificities of these immunohistochemical signals were verified by using Efhc1-deficient mice as negative controls. Results of Efhc1 mRNA in situ hybridization were also consistent with the immunohistochemical observations. Our findings raise “choroid plexusopathy” or “ciliopathy” as intriguing candidate cascades for the molecular pathology of epilepsies caused by the EFHC1 mutations.     

The Homer family proteins

The Homer family of adaptor proteins consists of three members in mammals, and homologs are also known in other animals but not elsewhere. They are predominantly localized at the postsynaptic density in mammalian neurons and act as adaptor proteins for many postsynaptic density proteins. As a result of alternative splicing each member has several variants, which are classified primarily into the long and short forms. The long Homer forms are constitutively expressed and consist of two major domains: the amino-terminal target-binding domain, which includes an Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) homology 1 (EVH1) domain, and the carboxy-terminal self-assembly domain containing a coiled-coil structure and leucine zipper motif. Multimers of long Homer proteins, coupled through their carboxy-terminal domains, are thought to form protein clusters with other postsynaptic density proteins, which are bound through the amino-terminal domains. Such Homer-mediated clustering probably regulates or facilitates signal transduction or cross-talk between target proteins. The short Homer forms lack the carboxy-terminal domain; they are expressed in an activity-dependent manner as immediate-early gene products, possibly disrupting Homer clusters by competitive binding to target proteins. Homer proteins are also involved in diverse non-neural physiological functions.     

Studies on the Metabolites of Cochliobolus miyabeanus

Ophiobolosin A and ophiobolosin B have been isolated as metabolites of Cochliobolus miyabeanus from the mycelia cultured on the different media. The former is identical with zizanin (C₂₉H₄₄O₅) and the new molecular formula, C₂₅H₃₈O₄ is presented. They have a biological effect to inhibit the germination and the growth of Oryzo sativa seeds and also an antifungal activity against Trichophyton spp. Here is reported the isolation, some physical and chemical properties and biological activities of ophiobolosins.     

Studies on Pyrethrosin

Pyrethazulene, an azulene produced by zinc-dust distillation of pyrethrosin, is not 2,4,8-trimethylazulene but a mixture of 1,4-dimethylazulene (major component) and other azulenes (minor components). 1,4-Dimethyl-6-ethylnaphthalene was obtained on Se-dehydrogenation of pyrethrosin.