Biomedical subjects

K Grundahl

Publications and source records attributed to K Grundahl.

4 recordsLinked to original sources

PubMed1994

Alternative splicing leads to two cholinergic proteins in Caenorhabditis elegans.

The cha-1 gene of Caenorhabditis elegans encodes choline acetyl-transferase (the acetylcholine synthetic enzyme). The C. elegans unc-17 gene encodes a synaptic vesicle-associated acetylcholine transporter. The two genes thus define sequential biochemical steps in the metabolism of the neurotransmitter acetylcholine. Cloning, sequencing, and molecular analysis of the unc-17 region indicate that cha-1 and unc-17 transcripts share a 5' untranslated exon, and the rest of the unc-17 transcript is nested within the long first intron of cha-1. Thus, two proteins with related functions but with no sequences in common are produced as a result of alternative splicing of a common mRNA precursor. The structure of this transcription unit suggests a novel type of coordinate gene expression, and a temporal processing model is proposed for the regulation of cha-1 and unc-17 expression.

Alleles↗

PubMed1994

Cloning and characterization of the choline acetyltransferase structural gene (cha-1) from C. elegans.

We have cloned the cha-1 gene from Caenorhabditis elegans using the method of transposon tagging, cha-1 is the structural gene for ChAT, the enzyme that synthesizes ACh. Sequence analysis of cDNAs predicts a protein of 71.5 kDa; comparison of the deduced amino acid sequence with ChAT sequences from other species confirms that cha-1 encodes ChAT. Comparison of cDNA and genomic sequences reveals that transcription is from right to left on the genetic map, and that some of the transcripts may result from trans-splicing of the 22-base spliced leader SL 1. The cha-1 gene is organized into 11 exons. The first exon contains only untranslated sequences, and is followed by an extremely long intron. The coding sequence of the cha-1 transcript is disrupted by mutations in the cha-1 gene. We have determined the sites of four transposon insertions and the end-points of two deletions that lead to the cha-1 mutant phenotype; one of the deletions appears to eliminate gene function completely. Comparison of the Drosophila, rat, and C. elegans genes reveals conserved motifs and conserved intron sites.

Amino Acid Sequence↗

PubMed1993

The Caenorhabditis elegans unc-17 gene: a putative vesicular acetylcholine transporter.

Mutations in the unc-17 gene of the nematode Caenorhabditis elegans produce deficits in neuromuscular function. This gene was cloned and complementary DNAs were sequenced. On the basis of sequence similarity to mammalian vesicular transporters of biogenic amines and of localization to synaptic vesicles of cholinergic neurons in C. elegans, unc-17 likely encodes the vesicular transporter of acetylcholine. Mutations that eliminated all unc-17 gene function were lethal, suggesting that the acetylcholine transporter is essential. Molecular analysis of unc-17 mutations will allow the correlation of specific parts of the gene (and the protein) with observed functional defects. The mutants will also be useful for the isolation of extragenic suppressors, which could identify genes encoding proteins that interact with UNC-17.

Acetylcholine↗

PubMed1993

Synaptic function is impaired but not eliminated in C. elegans mutants lacking synaptotagmin.

Synaptotagmin is an abundant synaptic vesicle-associated protein proposed to be involved in calcium-mediated neurotransmitter release. Our molecular and genetic results demonstrate that, although synaptotagmin is required for the proper function of the presynaptic nerve terminal in C. elegans, some neurotransmitter release persists in synaptogamin mutants. In C. elegans neurons, synaptotagmin is localized to regions known to be rich in synapses and appears to be associated with synaptic vesicles. Mutants defective in the synaptotagmin gene, called snt-1, exhibit severe behavioral abnormalities that are characteristic of deficiencies in synaptic function, including severe locomotion, feeding, and defecation defects. The mutants are defective in exocytosis, since they accumulate acetylcholine, and are resistant to cholinesterase inhibitors, but they nevertheless remain sensitive to cholinergic receptor agonists. In spite of these exocytic defects, snt-1 mutants are capable of coordinated motor movements, indicating that the mutants do not have a complete block of neurotransmitter release.

Amino Acid Sequence↗