Work

Selective disruption of the mammalian secretory apparatus enhances or eliminates calcium current modulation in nerve endings

Year: 2008

Type: article

Abstract: Modulation of secretion via G protein-coupled receptors (GPCRs) serves an important regulatory function in neuronal and nonneuronal secretory cells. Most secretory cells possess voltage-gated calcium channels, share homologues of the core complex of three proteins (the SNAREs) that constitute the secretory apparatus, and are modulated by GPCR activation. Activators of GPCRs generally inhibit the release of neurotransmitter substances to a maximum of only 50-60% of the control level, suggesting that complex protein-protein interactions may govern the efficacy of this form of modulation. In this article, molecular genetic approaches are used in combination with botulinum toxins (selective molecular scalpels that cleave the SNAREs at highly restricted loci) to address this issue. The results suggest that the cleavage of either of the plasma membrane SNAREs (syntaxin or SNAP-25) prevents modulation of calcium currents by A(1) adenosine receptors at mammalian motor nerve endings. In contrast, cleavage of the synaptic vesicle SNARE (synaptobrevin) in conjunction with deletion of the vesicle-docking protein Rab3A greatly enhances the efficacy of calcium current modulation.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.0708814105

Author: Eugene M. Silinsky

Institution: Northwestern University

Language: English

Topic: Cellular transport and secretion

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institute on Alcohol Abuse and Alcoholism, National Institute of Neurological Disorders and Stroke