Mutations in the unc-41 Gene Cause Elevation of Acetylcholine Levels

Abstract: Mutations in the Caenorhabditis elegans unc-41 gene result in an allele-dependent elevation of acetylcholine content. Eight recessive alleles ( cn252, e268, e399, e650, e1175, e1199, e1294, and e870 ) lead to phenotypes including uncoordinated locomotion, slow growth, a small mature body, and resistance to the acetylcholinesterase inhibitors as well as the elevation of acetylcholine content. The remaining two alleles, e554 and e1162 , exhibit normal acetylcholine levels but display the short-body phenotype in a semidominant way. To determine the localization of the elevated acetylcholine content, a method for the isolation of synaptic vesicles from C. elegans was established. The elevation of acetylcholine content in the unc-41 mutants is accompanied by the accumulation of synaptic vesicles. We propose that at least one function of the unc-41 gene relates to the release of neurotransmitters.     

Ddhd1 knockout mouse as a model of locomotive and physiological abnormality in familial spastic paraplegia

We have previously reported a novel homozygous 4-bp deletion in DDHD1 as the responsible variant for spastic paraplegia type 28 (SPG28; OMIM#609340). The variant causes a frameshift, resulting in a functionally null allele in the patient. DDHD1 encodes phospholipase A₁ (PLA₁) catalyzing phosphatidylinositol to lysophosphatidylinositol (LPI). To clarify the pathogenic mechanism of SPG28, we established Ddhd1 knockout mice (Ddhd1[−/−]) carrying a 5-bp deletion in Ddhd1, resulting in a premature termination of translation at a position similar to that of the patient. We observed a significant decrease in foot–base angle (FBA) in aged Ddhd1(−/−) (24 months of age) and a significant decrease in LPI 20:4 (sn-2) in Ddhd1(−/−) cerebra (26 months of age). These changes in FBA were not observed in 14 months of age. We also observed significant changes of expression levels of 22 genes in the Ddhd1(−/−) cerebra (26 months of age). Gene Ontology (GO) terms relating to the nervous system and cell–cell communications were significantly enriched. We conclude that the reduced signaling of LPI 20:4 (sn-2) by PLA₁ dysfunction is responsible for the locomotive abnormality in SPG28, further suggesting that the reduction of downstream signaling such as GPR55 which is agonized by LPI is involved in the pathogenesis of SPG28.     

Plasmid-controlled mercury biotransformation by Clostridium cochlearium T-2.

A strain of Clostridium cochlearium having methylmercury-decomposing ability was isolated. The ability was cured by the treatment with acridine dye and recovered by the conjugation of the cured strain with the parent strain. The cured strain then showed the activity to methylate mercuric ion as previously reported (M. Yamada and K. Tonomura, J. Ferment. Technol. 50:159-166, 1971). These results and the agarose gel electrophoretic pattern of the deoxyribonucleic acids from the lysates indicate a possible role of plasmids in controlling the mercury biotransformation of the two opposite directions in a single bacterial strain: methylation in the absence of the plasmid and demethylation in the presence of it. A possible mechanism for mercury resistance involving hydrogen sulfide is discussed.     

Renin and Angiotensin-Converting Enzyme in Human Neuroblastoma Tissue

High activity of renin was demonstrated in human neuroblastoma tissue. This activity was inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific action of proteases. The specific activity of renin was 122.8 ng of angiotensin I generated mg of protein-1 h-1. It shared some biochemical features with well-known kidney renin, such as molecular weight, optimum pH, the presence of trypsin-activatable inactive renin, and glycoprotein nature. Furthermore, angiotensin-converting enzyme (ACE) activity (2.64 nmol mg of protein-1 min-1) was found in the tissue. This activity was inhibited by captopril, a specific ACE inhibitor, or by omission of chloride ion. These results suggest that true renin in addition to ACE exists in human neuroblastoma tissue.